Involvement of T(H)1/T(H)2 cytokines in the pathogenesis of autoimmune skin disease-Pemphigus vulgaris.
Pemphigus vulgaris (PV) is classical example of antigen-driven severe autoimmune bullous skin disorder. Auto reactive T cells are critical for the induction and regulation of antibody production. With regard to cytokine production profiles, it has been reported that qualitative as well as quantitative alterations in cytokine production can result in activation of inefficacious effector mechanisms and therefore, complex and severe impairment in immune functions. The purpose of this study was to observe the alterations in the levels of T(H)1 [Interleukin-2 (IL-2), Interferon-gamma (IFN-gamma)] and T(H)2 (IL-4 and IL-10) cytokines in the sera from patients affected with PV and compared with Pemphigus foliaceus and healthy subjects. This work is aimed to comprehend the involvement of T(H)1 and T(H)2 cells as inflammatory infiltrate in the modulation of acantholysis and production of pemphigus lesions. Seventy PV, 13 PF and 50 healthy, age-matched individuals without any generalized skin diseases were included in this study. The diagnosis of PV and PF patients was confirmed by histopathology (hematoxylin and eosin) and / direct immunofluorescence. The levels of T(H)1 cytokines (IL-2 and IFN-gamma) and T(H)2 cytokine markers (IL-4 and IL-10) were estimated by high sensitivity ELISA kits. All patients with PV and PF showed significantly (p < 0.000) elevated levels of T(H)2 cytokines (IL-10 and IL-4) as compared with healthy controls. However, the mean concentration of T(H)1 cytokines (IL-2 and IFN-gamma) was significantly decreased in patients as compared to healthy individuals. Both T(H)1 and T(H)2 cytokines did not show any significant difference between PV and PF cases. Current concepts support the idea that PV, induced by autoantibodies against Dsg3, is the consequence of an imbalance between Dsg3-reactive T(H)2 and T(H)1 cells that may be critical for the maintenance of tolerance against Dsg3. Cytokine profile for confirmed PV cases showed direct evidences for involvement of T cell responses. Increase in IL-4 and IL-10 shows induction of T(H)2 cells in the pathogenesis of autoimmune disorders Pemphigus vulgaris. The decreased levels of IL-2 and IFN-gamma might demonstrate the inhibitory effects by IL-4 and IL-10, which suppress the expansion of T(H)1 population.
Satyam
Abhigyan
A
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Khandpur
Sujay
S
Sharma
V K
VK
Sharma
Alpana
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology; D002648:Child; D016207:Cytokines / Q000378:metabolism*; D051184:Desmoglein 3 / Q000276:immunology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000276:immunology / Q000503:physiopathology; D012871:Skin Diseases / Q000276:immunology / Q000503:physiopathology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation; D055815:Young Adult
D016207:Cytokines; D051184:Desmoglein 3; D016753:Interleukin-10; D015847:Interleukin-4