The regulatory effect of polychromatic (visible and infrared) light on human humoral immunity

Abstract

The immunological effects of visible and infrared light from laser and non-laser sources have remained insufficiently studied, which has restricted the use of light in the treatment of diseases associated with immune system disorders. The present randomized, placebo-controlled double-blind trial was designed to study changes in the humoral immunity of a large group of volunteers after exposure of a small body area to polychromatic visible and infrared polarized (VIP) and non-polarized (VInP) light (400–3400 nm, 95% polarization, 40 mW cm⁻², 12 J cm⁻² and 400–3400 nm, no polarization, 38 mW cm⁻², 11.2 J cm⁻², respectively). Serum immunoglobulins (Ig) M, A, and G were determined turbidimetrically, and the immune complexes (ICs) by precipitation with 5% polyethylene glycol and subsequent spectrophotometric analysis. A single VIP irradiation induced an average rapid rise in serum IgM levels of 13% (p < 0.05). By the end of the 10 day course, it had exceeded the baseline level by 26%, with an increase in IgA levels of 17 and of 12% (p < 0.05) one week after the last session. In subjects with a high IC content, it decreased rapidly to the normal level. A single exposure of volunteers to VInP light rapidly produced changes similar to those observed on VIP irradiation, but with an increase in IgM 2.3 to 3 times lower, independent of the initial levels. On the other hand, VInP light exposure decreased the IC content more than VIP light.

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Introduction

The immunological effects of visible and infrared light emitted by laser and non-laser sources still remain poorly studied.^1,2 The available data indicate a pronounced positive effect of visible and IR light on the immune system.^1,2 However, the considerable variations in the results with the lack of experimentally substantiated concepts of systemic mechanisms of immune system response to irradiation of small areas of the human body surface has helped prevent the widespread clinical application of visible and IR light for treatment and prevention of diseases involving the immune system.

Characteristics specific to laser light, such as coherence and monochromaticity, are no longer currently considered as necessary conditions to achieve general phototherapeutic effects, and the combination of visible and IR light has become a popular phototherapeutic tool.^3–10 The concept of the polarization of light, however, remains a subject for discussion.^11–15

In the past few years, our laboratory has been dedicated to the study of some parameters of human homeostasis following percutaneous irradiation with polychromatic visible and IR light, simulating a large portion of the natural terrestrial solar spectrum (400–3400 nm), but with the addition of a high degree of polarization, as found in many therapeutic laser systems (VIP light). Given that visible and IR radiation penetrates into skin, at least as far as the superficial blood vasculature, we have shown that VIP light produces structural/functional changes of components of a comparatively small amount of blood, and that these changes are almost immediately translated to the entire volume of circulating blood.^16–20 A consequence of changes in the entire volume of peripheral blood is the development of such systemic effects as improvement of haemorheology, beneficial alterations to the transport, metabolic, growth-promoting, and immunological properties and functions of blood. VIP light has been shown to be capable of altering the mononuclear cell membrane phenotype, inducing an immediate rise in the phagocytic capabilities of monocytes and granulocytes, modulating the activity of natural killer cells, and causing blast-transformation of lymphocytes.^{16–19,21,22}

The goals of the present study were, first, to study the effects of VIP light on humoral immunity in a large group of volunteers and, second, to find out if non-polarized broadband light (VInP) would be capable of inducing similar immunity-related changes.

Materials and methods

Volunteers and blood samples

Apparently healthy, randomly-selected 20–65 year-old volunteers of both sexes participated in our trials. They were randomly divided into three groups, two experimental groups and one untreated control group. The ratio of sexes and ages of the volunteers in each group were similar. Criteria for elimination from the experiment were allergic reactions and chronic somatic diseases in anamnesis. For two weeks of the experiment, repeated medical examinations were performed, which allowed the presence of acute inflammatory diseases in the subjects to be ruled out.

The VIP group (22–29 subjects) was treated with VIP light for 10 days, once per day on a lumbar-sacral area (D = 15 cm). The VInP group (24–26 individuals) received a single irradiation in the same zone. The blood for the studies in the VIP group was drawn as follows: 30 ml before the start of the trials, 15 ml at 0.5 and 24 h after the 1st irradiation, 15 ml at 24 h after the 4th and 9th procedure. In some subjects from this group, the after-effects of the phototherapeutic regimen were studied one week after the end of the treatment course. In the VInP group, blood was drawn immediately prior to, and 0.5 and 24 h after the single VInP irradiation. Members of the control (placebo) group (n = 14) underwent mock irradiation and the blood for studies was collected at the same time periods and in the same volume as for the light-irradiated volunteers. The participants in the trial were not informed prior to the study as to which group they belonged.

Blood was drawn from the cubital vein under standard conditions, in the morning, in a room with a dim light, as intense artificial illumination might have affected blood parameters.^23,24 After clotting of blood, serum was separated by centrifugation for 10 min at 1000g (Becton Dickinson serum separator tubes, Franklin Lakes, NJ, USA). Serum samples were coded and frozen at −20 °C for a subsequent double-blind analysis by an independent researcher.

Taking into account the significant seasonal dependence of immunological blood parameters and the decrease in the photoreactivity of blood cells and proteins in summer,^25,26 the volunteers were irradiated from November to March inclusive.

Light sources

VIP light (400–3400 nm, 95% polarization, power density 40 mW cm⁻²) was delivered by a Bioptron-2 device (Bioptron AG, Wollerau, Switzerland). After removing the polarizing elements from the Bioptron apparatus, VInP light of the same spectral composition and with a similar power density (38 mW cm⁻²) was obtained. At a distance of 20 cm from both light sources and at an irradiation duration of 5 min, doses of the VIP and VInP light amounted to 12 and 11.2 J cm⁻², respectively. The same system fitted with an opaque filter was used for the mock irradiation of the placebo group.

Determination of the serum immunoglobulin content

Test summary. The serum content of immunoglobulins (Ig) M, A, and G was determined turbidimetrically²⁷ using a Kone specific automatic analyzer and the Konelab test systems (Thermo Clinical Labsystems, Vantaa, Finland). This method is based on the ability of serum Ig to interact in the liquid phase with specific antibodies and to form a precipitating antigen–antibody complex. Immunoprecipitation produced an increase in the optical density of the sample in proportion to the concentration of the corresponding Ig, and was recorded turbidimetrically at a wavelength of 340 nm.

Testing procedure. The test systems contained porcine antisera (antibodies to IgM, A, and G); buffer [0.05 mol l⁻¹ TRIS buffer, pH 7.2; 5% polyethylene glycol (PEG); 0.1% sodium azide], specimen diluent (0.01 mol l⁻¹ phosphate-buffered saline, 0.1% sodium azide), and a SpeciCal protein calibrator lyophilized at an Ig concentration indicated in the annotation and certified according to the certified reference material (CRM 470) of the Committee of Plasma Protein Standardization of the International Federation of Clinical Chemistry (IFCC). Six standard dilutions of the calibrator were prepared automatically.

All serum samples were defrosted and submitted to a simultaneous automatic analysis. They were diluted 1 ∶ 51 with the diluent, then 50 µl (for determination of IgA), 25 µl (IgG), or 100 µl (IgM) were mixed in cuvettes with 400 µl of the buffer; in the standard, the same amount of the diluted calibrator was used instead of the serum. After 10 min of incubation, the initial absorption was measured turbidimetrically, then 50 µl of the specific antiserum previously diluted 1 ∶ 3 with buffer were added automatically to the studied and control samples. The samples were stirred, then the turbidimetric analysis was repeated after 2 min, and the difference in optical density between the final and initial measurements was calculated. Based on the obtained data, a calibration curve was constructed by the analyzer, the curve being the single standard for this series of experiments. Results were calculated automatically, using the calibration curve, and were expressed as units of concentration, g l⁻¹. To verify the accuracy and reproducibility of results, control sera with normal (Nortrol) and decreased (Abtrol) concentrations of the studied Ig (Konelab) were used.

Sensitivity. According to the manufacturer’s data, the area of the measured concentrations are: for IgA 0.4–7.0 g l⁻¹ (the normal values for adults are 0.9–4.5 g l⁻¹), for IgG 3.0–50.0 g l⁻¹ (8–18 g l⁻¹), for IgM 0.2–5.0 g l⁻¹ (0.6–2.5 g l⁻¹).

Determination of the immune complex content

The immune complex (IC) level in blood serum was determined by the standard method of precipitation with 5% PEG.²⁸ Serum was diluted two-fold with a borate buffer, and 20 µl was introduced into each well of a flat-bottomed plate (Medpolymer, St. Petersburg, Russia) for enzyme-linked immunosorbent assay (ELISA). They were next added to 200 µl of 5% PEG (M_w 6000 g mol⁻¹). As a control, several wells were filled with 200 µl of borate buffer instead of PEG. The plates were incubated on a shaker for 1 h at room temperature, then studied spectrophotometrically at 450 nm (microplate reader; Organon Teknika, Oss, The Netherlands). The amount of ICs was determined subtractively by comparing the optical densities in the experimental and control specimens, and expressed using relative units (the normal values for adults are 0–60 rel. units).

Statistical analysis

Statistical processing of the results was performed by parametrical and non-parametrical methods for matched (dependent) pairs of results (2-tailed Student's t-test and Wilcoxon test). Correlations of effects with the initial level were calculated by the Pearson method.

Results

Effects of single and multiple sessions with polarized light

The baseline levels of IgG, IgA, and IgM in the blood of the studied volunteers varied by factors of 2, 4, and 7, respectively; however, in most subjects, the levels were within the normal limits.

As seen from Fig. 1(A), both in the main and in the placebo groups, there were no statistically significant changes in the mean IgG level at all time periods of testing. Nevertheless, correlation analysis revealed an inverse (negative) dependence of the IgG content changes on its initial level on the 5th and 10th days: correlation coefficients r = −0.57, p < 0.01 and r = −0.42, p < 0.05, respectively. We used the median method to divide all volunteers into 2 subgroups according to their initial IgG level (higher and lower than the median) and analyzed the dynamics. The mean IgG content in both subgroups was not seen to change in a statistically significant manner after VIP sessions. Nor did it change in the placebo group; however, in this case, the dependence on initial parameters was not recorded.

Fig. 1 Dynamics of the IgG (A) and IgA (B) contents [(m ± SE)/g l⁻¹] in the blood serum after daily irradiation of the sacral area with polychromatic visible and infrared polarized (VIP) light at a therapeutic dose level (see text for details). The number of VIP-irradiated subjects was 25 (A) and 29 (B). The placebo (control) group (n = 14, A, B) was mock irradiated and the blood for studies was withdrawn at the same time periods and in the same volumes as for the irradiated individuals. Asterisks indicate statistically significant differences from the initial level (p < 0.05).

The IgA content did not changed in VIP-irradiated subjects up to the 10th day, when it increased significantly by 3–94% from the initial level in different individuals, and by 17%, on average, in the group [Fig. 1(B)]. No marked dependence on initial parameters was revealed. In 9 subjects, analysis of delayed changes in the IgA content showed maintenance of the effect of the VIP course one week after the 10th session, with a significantly higher level of 12% compared with the pre-irradiation levels [Fig. 1(B)]. There were no changes in IgA content in the control group.

The baseline level of IgM in the blood of 23 subjects varied within normal limits and was, on average, 1.11 ± 0.09 g l⁻¹; three subjects had an elevated IgM content as compared with the norm (2.97 ± 0.22 g l⁻¹). The data on the mean values showed that the normal IgM level increased significantly as soon as 0.5 h after the 1st irradiation, rose after each subsequent procedure, and, by the end of the course, exceeded the initial values in individuals by 6–200%, and by 26%, on average, for the group (Fig. 2). One week after the 10th session, the IgM levels had returned to the initial values. The dynamics of IgM changes in the control group were quite different (Fig. 2): after a slight, although statistically significant decrease in the IgM content following the 1st mock irradiation, the content returned to the initial level and did not change until the end of the study period. In 3 subjects with initially elevated IgM contents, a tendency was recorded for reduction, on average, from 2.97 to 1.79 and 2.03 g l⁻¹ at 0.5 and 24 h, respectively, after the 1st VIP session and then to 1.68 and 2.27 g l⁻¹ after 4 and 9 daily VIP sessions, respectively, i.e. 57–76% of the IgM content before the VIP treatment.

Fig. 2 Dynamics of the IgM content [(m ± SE)/g l⁻¹] in the blood serum after daily irradiation of the sacral area with polychromatic visible and infrared polarized (VIP) light at a therapeutic dose level. The number of VIP-irradiated subjects was 23, with 14 in the placebo group. Asterisks indicate statistically significant differences from the initial level (single asterisk: p < 0.05; double asterisk: p = 0.01).

Analysis of individual changes in both subgroups taken together reveals that whereas in the irradiated volunteers they depend inversely on the initial parameters, i.e. having a regulated characteristic (the correlation coefficient r varied at the different time periods from −0.44 to −0.70, p < 0.05, p < 0.01), in non-irradiated subjects, this regularity was not observed. It should be noted that the fast changes in the IgM content after the 1st irradiation have not only a regulatory, but also a normalizing character, as the dispersion index (Fisher coefficient) reached statistically significant values: 2.17 in 0.5 h and 2.36 in 24 h, p < 0.05. This regularity is shown in Fig. 3.

Fig. 3 Regulatory and normalizing effect of a single VIP light irradiation on the blood serum IgM levels [(m ± SE)/g l⁻¹]. When dividing all the subjects into 2 subgroups according to the character of changes at 0.5 (A) and 24 h (B) post-irradiation, a decrease in the IgM level can be clearly seen in those subjects with a relatively high initial level (n = 8), and an increase in those subjects with a relatively low initial level (n = 15), showing, along with the dispersion analysis data, the normalizing trend of VIP phototherapy.

The individual blood serum IC levels in the volunteers varied by a factor of 20, but corresponded, on average, to the normal value for healthy subjects. Depending on the initial IC content, the volunteers were divided into 2 subgroups: individuals with normal values and those with values exceeding the norm (the 1st and 2nd subgroups, respectively). Members of the 1st subgroup showed no significant changes of the IC level for the 10 days of observation, both in the main and in the control groups. However, analysis of individual results revealed that changes did take place in the irradiated subjects, their character depending on the initial IC content, which varied 9-fold in this group: as a rule, a decrease occurred for initially high (but normal) parameters, while an increase was noted for those with initially decreased levels (r = −0.48 and −0.50, p < 0.01, in 0.5 and 24 h, respectively). No such regularity was seen in the control group. Using the median method, we subdivided subjects with normal IC content into groups A and B—relatively low (below the median) and relatively high (above the median) contents, respectively. Whereas there were no significant changes in group A [Fig. 4(A)], a statistically significant decrease in the IC level occurred in subjects of group B: on average, 26% on the 5th day and 35% one week after the end of the VIP course [Fig. 4(B)]. In the placebo A and B groups, no significant changes in IC levels were observed [Fig. 4(A) and (B)].

Fig. 4 Dynamics of the IC content [(m ± SE)/rel. units] in the blood serum of subjects with normal (A, B) and greater than normal (C) initial levels after daily irradiation of the sacral area with VIP light. On analyzing the results, the members of the VIP-irradiated and placebo groups with normal levels of ICs were subdivided by the median method into groups A and B—relatively low (<median) and relatively elevated (>median) parameters, respectively. The number of VIP-irradiated subjects in each group was 11 (A), 12 (B), and 5 (C), and in the placebo group 6 (A) and 5 (B). Asterisks indicate statistically significant differences from the initial level (single asterisk: p < 0.05; double asterisk: p < 0.01); plus: p = 0.06.

A significant decrease in the IC content after exposure to VIP light also took place in all volunteers with increased, as compared with normal, IC levels (>60 rel. units): by the end of the phototherapeutic course, the IC content was reduced from 84 to 68 rel. units (i.e. by 19%) and approached the upper norm level [Fig. 4(C)].

Effect of single sessions with non-polarized light

Since there are no clinical reports on the results of repeated treatment sessions using non-polarized visible and IR (VInP) light, we recorded the effects of a single procedure, testing the parameters pre-irradiation, then at 0.5 and 24 h after the single treatment session. The initial parameters and the range of individual variability in the VInP subjects were comparable with those in the VIP-irradiated group, with no significant differences in any of the baseline values.

On finding no statistically significant changes in the IgG and IgA contents after a single VInP irradiation, we started analyzing two other parameters, IgM and ICs, as they changed almost immediately after the 1st VIP session.

The IgM content in the blood serum of 23 volunteers of this group corresponded to the norm (1.21 ± 0.09 g l⁻¹), while in 3 individuals, it was much higher (3.36 ± 0.31 g l⁻¹). It was found that the non-polarized light produced no statistically significant increase in the IgM content in the 23 normal level subjects, both at 0.5 and 24 h, whereas the tendency for an increase was obvious (Table 1). Indeed, a rise of the IgM content was seen at these time periods with the same frequency as in the VIP group, but the degree was 2.3–3 times lower. Also less pronounced was the decrease in the IgM level in VInP subjects with initially high values, from 3.36 to 2.59 and 2.68 g l⁻¹ at 0.5 and 24 h, respectively, i.e. 77–80%. As a whole, the regulatory and normalizing influence on the IgM content observed in VIP-irradiated subjects was not apparent for VInP-irradiated volunteers.

Table 1 Comparison of changes in the blood serum IgM and IC levels in volunteers with initially normal levels after a single exposure to polarized and non-polarized light

				Increase	Decrease	No change
Parameter	Light	Time after irradiation/h	Content (m ± SE)^a	Incidence (%) and mean extent [Δ (%)]	Incidence (%) and mean extent [Δ (%)]	Incidence (%)
a Asterisks indicate a statistically significant difference from the initial level (single asterisk: p < 0.05; double asterisk: p = 0.01).
IgM (g l^−1)	Polarized	0 (before)	1.11 ± 0.09
	n = 21	0.5	1.25 ± 0.09*	65 [+39]	18 [−31]	17
		24	1.31 ± 0.08**	58 [+44]	26 [−8]	16
	Non-polarized	0 (before)	1.21 ± 0.09
	n = 23	0.5	1.24 ± 0.10*	61 [+13]	39 [−24]	0
		24	1.27 ± 0.09	61 [+19]	35 [−18]	4
ICs (rel. units)	Polarized	0 (before)	35.8 ± 3.26
	n = 23	0.5	37.5 ± 3.58	50 [+13]	50 [−17]	0
		24	36.5 ± 3.63	59 [+43]	41 [−37]	0
	Non-polarized	0 (before)	30.9 ± 2.93
	n = 21	0.5	34.9 ± 2.52	53 [+80]	42 [−20]	5
		24	30.8 ± 2.60	42 [+61]	58 [−19]	0

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On the other hand, the effects of VInP treatment on the IC level were quite comparable with those resulting from irradiation with polarized light, both in volunteers with initially normal parameters and in those with high (above the norm) IC contents (Table 1, Fig. 5). Also obvious was the inverse dependence of the effect on the initial parameters, which demonstrates the regulatory effect of VInP light on the blood IC level (r = −0.54, p < 0.01 and r = −0.52, p < 0.05, at 0.5 and 24 h, respectively). Therefore all volunteers with normal IC levels were subdivided by the median method into groups A and B with relatively low (below the median) and relatively high (above the median) IC contents. As can be seen in Fig. 5(A) and (B), a decrease in IC content occurred in group B, by 16%, on average, as early as 24 h after the VInP session, whereas no changes were recorded in group A. The reduction in IC content was also observed for 4 volunteers with abnormally high IC values, by 42%, on average, after 24 h [Fig. 5(C)].

Fig. 5 Dynamics of the IC content [(m ± SE)/rel. units] in the blood serum of subjects with normal (A, B) and greater than normal (C) initial levels after a single irradiation of the sacral area with VInP light. On analyzing the results, members of the VInP-irradiated and placebo groups with normal levels of ICs were subdivided by the median method into groups A and B—relatively low (<median) and relatively elevated (>median) parameters, respectively. The number of the VInP-irradiated subjects in each group was 9 (A), 9 (B), and 4 (C), and in the placebo group 6 (A) and 5 (B). Asterisks indicate statistically significant differences from the initial level (p < 0.05)

Discussion

This work shows that both a single irradiation of a small body surface area with VIP light and a course of 4–9 daily phototherapeutic sessions produce significant systemic changes in some humoral immunity-related parameters. The most ‘reactive’ was IgM, levels of which rose by statistically significant amounts as early as 0.5 h after the single VIP irradiation, and which by the end of the 10 day course exceeded the initial levels by 26%, without leaving the normal limits. At all the time periods studied, the initially low parameters increased, while the initially elevated ones decreased, resulting in a fall in the dispersion of the studied parameter, which indicates that VIP light has not only a regulatory, but also a normalizing, effect on the IgM content. By the end of the 10 day phototherapeutic course, an increase in the IgA level (17%, on average) had also occurred, this effect being maintained one week after the end of the treatment. Moreover, daily exposure to VIP light induced a decrease in the IC level: this effect was particularly pronounced in subjects with initially high IC contents.

The results obtained agree with the data of other authors reporting the normalization of Ig levels after irradiation with visible and IR light from low-intensity lasers.^{2,4–7,15,29–34} The similarity of the effects of visible and IR radiation and the efficiency of their combined use have been reported previously.^4–7 Fenyo irradiated poorly healing trophic wounds with polychromatic polarized light with spectral characteristics (400–3000 nm) very similar to the broad waveband used in the current study and found an increase of the IgM, IgA, and IgG contents.¹¹ On the background of the rather controversial data published on the effect of laser therapy on IgG and IgM dynamics, most authors report a pronounced increase in the IgA content, both of serum levels and also of secretory IgA (sIgA). It has been suggested that this mechanism might be responsible for the high efficiency of light treatment in prevention of acute respiratory diseases,⁵ as well as in therapy of pathologies of respiratory and digestive organs,^4,6,30,32,34 because most of these conditions are accompanied by decreased IgA and sIgA contents. Several publications indicate normalization of the IC content after a course of treatment sessions with red and/or IR laser light in patients with bronchial asthma⁷ and rheumatoid arthritis,³⁵ as well as for the pre-surgery preparation of cardiovascular patients.³¹ According to the above papers, the decrease in the IC content correlated with the clinical effect.

In summarizing the many years experience of the use of therapeutic lasers, we would like to emphasize that the effect of low intensity laser irradiation is clearly modulatory in character, depending on the initial parameters.^4,15,36 In the present study, we have revealed the regulatory effect of polychromatic light.

As regards the mechanisms of stimulation of antibody production after treatment with VIP light, they could be compared in some ways to the response following exposure to thymus-independent antigens, when B-lymphocytes are activated, without any cooperation with T-helpers, which results in relatively early production and secretion of IgM. In this case, there is neither any change of Ig isotypes (i.e. the response is restricted to the synthesis of IgM), nor any increase of the affinity of antibodies in the dynamics of the response, with no formation of memory B-cells. Such response is characteristic of CD5+ B-1 cells.³⁷ However, some thymus-independent antigens are able to induce polyclonal activation of B-cells,³⁷ which may account for the synthesis of other Ig isotypes.

Low affinity IgM, the first line of defence against bacteria, appear as early as the 2nd day of the immune response.³⁷ According to our data,¹⁷ irradiation of the human body surface with VIP light is accompanied by an immediate increase in the expression of the membrane B-lymphocyte marker CD20, which might be considered as a sign of activation of these cells. The rapid initiation of synthesis and secretion of antibodies by B-lymphocytes could be mediated through the mechanism of visible and IR light photoactivation of the NADPH–oxidase complex in blood cells, and subsequent formation by these cells of reactive oxygen species (ROS). This nucleotide-containing flavocytochrome located in the plasma membrane of many cells, including B-lymphocytes and other blood cells, has a wide absorption spectrum and can be directly activated with light of different spectral ranges.^38–41 The ROS thus formed are able to interact directly with membrane receptors and initiate an autocrine and paracrine redox activation (regulation) of components of signal transduction; owing to this, activation of the synthesis of macromolecules occurs, concomitant with activation or retardation of cell proliferation, differentiation, and apoptosis.^38–41 The question of the mechanisms by which IgM appears almost immediately (within 0.5 h) after VIP irradiation remains, at present, unanswered. It cannot be ruled out that this phenomenon is due to the shedding of glycoproteins from the surface of mononuclear cells, as we previously reported following UV irradiation of healthy human blood.²⁶ According to Mester et al.,¹⁵ the rapid increase in IgM content after treatment with He–Ne laser light might be a consequence of their desorption from the surface of B-lymphocytes.

The increase in IgA production at the end of the phototherapeutic course might be a consequence of a rapid rise in blood serum IL-10 levels in VIP light-treated volunteers, in addition to TGF-β1 at originally low levels.²¹ These cytokines are known to play a certain role in switching antibody synthesis to the IgA isotype.^37,42

The mechanism of the rapid fall of peripheral blood IC levels in subjects with high levels could possibly be due to the photoenhancement of the ligand-binding ability of erythrocytes which have a particular affinity for ICs and, via receptors for complement, bind ICs to their surfaces and carry the ‘captured’ ICs to the liver and spleen, where they are destroyed by tissue macrophages.⁴³ The phenomenon of a significant increase in the expression of erythrocyte membrane receptors has been previously reported in our studies after exposure of blood to some photostimuli, including VIP light.^19,44,45 Furthermore, it has been shown that complexes with antibodies of subtypes IgG1 and IgG3 are directly bound to the membranes of monocytes/macrophages via the corresponding FcRII, and which then destroy the ICs through phagocytosis.⁴⁶ An increase in the monocyte and granulocyte phagocytic activity after irradiation with VIP and UV light has also been demonstrated in our laboratory.^16,18,26 However, we cannot rule out the possibility of the stimulatory effect of VIP irradiation on the activity of some components of the complement system, which is reduced in some diseases and leads to impaired elimination of ICs. Such effects of non-coherent UVC and coherent red light have been described in the literature.^15,25

Taken as a whole, the results obtained in the current study substantiate the possibility of using a phototherapy regimen based on VIP light to correct a deficient primary anti-infection response and to improve mucosal defence mechanisms through increasing the levels of, respectively, IgM and IgA. Decreased IC levels may be considered as the result of the photoactivation of an important antigen-elimination mechanism and of eventual enhancement of the anti-infection immune response. It is well known that ICs are able to produce local and generalized toxic reactions and to play a pathogenetic role in the development of several diseases of infection-allergic nature, amongst others.^37,43 Therefore, the photomediated elimination of ICs from the peripheral circulation in subjects with elevated levels would appear to be prognostically favorable.

From these data, a treatment regimen involving VIP irradiation of the human body surface is an efficient method for correction of humoral immunity. Further specific studies are required to ascertain the degree of the immunomodulatory effects induced by non-polarized light of the same spectral range as the VIP light used in the present study. However, the potential phototherapeutic utility of both VIP and VInP light has been shown in the current study, and in our previous report,¹⁸ which clearly demonstrate the similarity of effects induced by a single exposure to VIP and VInP light. If we consider that the studied waveband, 400–3400 nm, represents a significant part of the terrestrial solar waveband, with the exception of the UV spectrum, then elucidation of the regulatory actions of this polychromatic light on the human immune system should be of wide-ranging biological significance.

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