UVB exposure‐induced systemic modulation of Th1‐ and Th2‐mediated immune responses

Abstract

Exposure to ultraviolet light, especially UVB wavelengths, can impair immune responses in animals and humans. It is remarkable that this immunomodulation is not restricted to the exposed skin but is also found at other sites, i.e. systemic (distant) immunosuppression. A frequently proposed hypothesis is that UVB exposure inhibits, specifically, T helper 1 (Th1)-mediated immune responses. The major reason for this is that contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH), both Th1-mediated immune responses, are very sensitive to UVB. For this reason these models are frequently used for photoimmunology studies. In the present study, the effects of UVB exposure were investigated in classical models for Th1-mediated immunity, i.e. CHS models in which picrylchloride or oxazolone were used as low-molecular-weight chemical antigens. In these models, CHS responsiveness and cytokines were measured, the latter by both reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The CHS responses to both contact sensitizers (picrylchloride and oxazolone) were suppressed significantly by pre-exposure to repeated suberythemal UVB exposure. Interferon-gamma (IFN-gamma), interleukin (IL)-12 and IL-4, but not IL-10, were detectable in spleen and draining lymph nodes of sensitized BALB/c mice. Repeated UVB exposure prior to sensitization at a distant locus inhibited both IFN-gamma and IL-12 but not IL-4. In BALB/c mice sensitized with ovalbumin (OVA) in the absence of complete Freund's adjuvant, a model for Th2-mediated immunity, OVA-specific serum IgE and cytokine profiles in the spleen were analysed. Sensitization did lead to a significant increase in OVA-specific IgE serum titres. Pre-exposure to UVB resulted in a decreased OVA-specific IgE serum titre. Both RT-PCR and ELISA showed increased levels of IFN-gamma, IL-4 and IL-10 in the spleens of OVA-sensitized mice. The production of IFN-gamma and IL-4 was not affected by UVB pre-exposure. In contrast, the production of IL-10 was significantly increased. This was probably caused by an up-regulation of Th2 cells. It is remarkable that IFN-gamma is significantly suppressed by UVB in Th1-mediated immune reactions but not in Th2-mediated immune reactions where it even appears to increase. IL-10, which is up-regulated by UVB pre-exposure and produced by, among others, Th2 cells, may represent a shift from Th1- to Th2-mediated immune mechanisms. However, IL-10 can also inhibit Th2 responses, which might be the reason for a decreased IgE titre in the Th2 model. From the results of this study it is concluded that UVB exposure prior to sensitization/immunization not only inhibits Th1-mediated but also Th2-mediated immune responses.

Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence.

“…The corresponding inverse association between UVR levels in Australia and type 1 diabetes prevalence is also consistent with previous photoimmunologic work showing that ultraviolet B irradiation has systemic as well as local immunosuppressive effects in humans and animals Duthie et al 1999;Garssen et al 1999;Sleijffers et al 2001), as does also ultraviolet A irradiation (Nghiem et al 2001). UVR exposure may be protective against Th1-mediated disorders such as type 1 diabetes by downregulating Th1 autoimmune responses by several different immunoregulatory mechanisms Duthie et al 1999;Ponsonby et al 2002).…”

“…We are uncertain of the significance of this finding, particularly as the prevalence increase over the UVR range was only low. UVR-induced Th2 upregulation is one possibility, but UVR can also suppress Th2 responses (Garssen et al 1999). In addition, the contribution of regional allergen levels to asthma prevalence could be important.…”

“…However, recent work has cast doubt on the mutual antagonism of Th1 and Th2 cytokine expression, particularly in humans (Davidson and Diamond 2001;Mackay 2000;Platts-Mills 2002;Platts-Mills et al 2001). Ultraviolet B, particularly through interleukin 10, can inhibit both Th1-and Th2-mediated immune responses in mice (Garssen et al 1999). In children, asthma can coexist with Th1-type disorders such as type 1 diabetes, RA, and celiac disease, suggesting a common environmental influence (Kero et al 2001).…”

Lack of response of INT-407 cells to the presence of non-culturableCampylobacter jejuni

“…INT-407 cells without addition of bacteria were used as control. IL-8 concentrations were determined in triplicate using an IL-8 ELISA according to Garssen et al [31].…”

Effects of Fumaria parviflora L on Uremic Pruritus in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

“…Additional evidence regarding this immunohypothesis is the decrease in UP following ultraviolet B (UVB) irradiation to even half of the body (35). This result may be due to the inhibition effect of UVB on Th1-mediated immune reactions (36). Our study proved that IFN-γ level decreased significantly in HD patients who received FP compared with those who received placebo.…”