Cytokine Polymorphisms Play a Role in Susceptibility to Ultraviolet B-Induced Modulation of Immune Responses after Hepatitis B Vaccination

Abstract

UVB exposure can alter immune responses in experimental animals and humans. In an earlier human volunteer study, we demonstrated that hepatitis B-specific humoral and cellular immunity after vaccination on average were not significantly affected by UVB exposure. However, it is known that individuals differ in their susceptibility to UVB-induced immunomodulation, and it was hypothesized that polymorphisms in specific cytokines may play a role in this susceptibility. In this respect, we previously demonstrated that immune responses after hepatitis B vaccination are influenced by the minor allelic variant of IL-1β in the general population. For all volunteers, single nucleotide polymorphisms were determined for the following UV response-related cytokines: IL-1 receptor antagonist (+2018), IL-1α (+4845), IL-1β (+3953), TNF-α (−308), and TNF-α (−238). Exposure to UVB significantly suppressed Ab responses to hepatitis B in individuals with the minor variant for the IL-1β polymorphism. Increased minimal erythema dose values (just perceptible), which resulted in higher absolute UVB exposures, were observed in the same individuals. There were no associations observed between UVB-induced immunomodulation and the other cytokine polymorphisms examined. This study indicates that individual susceptibility to UVB radiation needs to be considered when studying the effects of UVB in humans.

Association of -238G/A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population

“…Patients with acute and chronic hepatitis B have an elevated plasma concentration of TNF-α [7,8] . Some individual differences in cytokine production may be related to genetic components, and certain polymorphism alleles may be associated with higher or lower levels of TNF-α production, which has been ascribed to polymorphisms within the regulatory regions of cytokine genes [9][10][11][12][13][14] . There were some studies about the association of TNF-α gene promoter polymorphism with progress of the disease [13,15] , but ethnic difference could lead to different results.…”

Ultraviolet Light and Resistance to Infectious Diseases

“…We demonstrated within our human volunteer study that both the humoral and cellular immune response to HBsAg were significantly increased in individuals possessing the minor allelic variant of IL-1β (+3953) (Yucesoy et al, 2002). However, possession of this minor allelic variant of IL-1β resulted in significantly suppressed antibody responses to hepatitis B after exposure to UVB (Figure 2) (Sleijffers et al, 2003b). Increased minimal erythema dose values, which resulted in higher absolute UVB exposures, were observed in these same individuals.…”

“…Volunteers homozygous for the minor allelic variant of the IL-1β polymorphism (2.2) demonstrated 7-11 times (depending on the time-point) lower anti-HBs levels compared to control volunteers with the same genotype. (after Sleijffers et al, 2003b). four-fold and heterozygous cells produce approximately 2-fold more IL-1β compared to individuals homozygous for the wildtype allele (Pociot et al, 1992).…”

Immunotoxicology

“…For a review of the influence of endogenous and environmental factors on vaccination responses see [81]. The importance of genetic factors on the response to a vaccine is shown by the role of CYTOKINE polymorphisms in the susceptibility of humans to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination [82].…”