Interleukin-38
Interleukin-38 (IL-38) is a member of the interleukin-1 (
Discovery
IL-38 probably originated from a common ancestral gene - an ancient IL-1RN gene.
Processing and signaling
According to consensus of cleaving site of IL-1 family, it is predicted that two amino acids (AA) should be removed to generate a processed 3-152AA IL-38 protein. The protease which cleaves IL-38 is still unknown as well as it is still not known which form of IL-38 is the natural variant present in the human body. It was reported that 20-152AA IL-38 form has increased biological activity.[9]
IL-38 has non-characteristic dose-response curve and it binds to IL-36R (IL-1R6). This cytokine is blocking
Role in disease
Studies showed that IL-38 could play an important role in rheumatic diseases.[11][12][13] IL-38 is also one of the five proteins which are related with C-reactive protein (CRP) levels in the serum.[14] The association of IL-38 with CRP could mean that IL-38 will play role also in inflammatory diseases as cardiovascular disease.
Function
The observation of knockdown of IL-38 with
Also when spontaneous murine model of systemic lupus erythematosus (SLE) was treated with recombinant IL-38, mice had less symptoms like proteinuria and skin lesions.[17] Also serum levels of IL-17 and interleukin-22 were lower in these mice what approves in vitro observation that IL-38 could inhibit Th17 responses. Patients with SLE had higher concentrations of IL-38 in the serum than healthy patients and also patients with active disease had higher concentrations of IL-38 in the serum than patients with inactive form.[15]
Sjogren's disease is disease related to SLE. Biopsy of gland of patients with primary Sjogren's disease shows that the expression of IL-38 was increased here. For modulation of this disease is important axis of IL-36. IL-38 is probably antagonist of IL-36 signaling similar as IL-36Ra what can play an important role in the pathogenesis of this autoimmune disease.[18]
IL-38 was found also in the synovium of patients with rheumatoid arthritis and as well in mice with collagen-induced arthritis (CIA). IL-38 concentrations correlated with IL-1β. The overexpression of IL-38 in murine model of arthritis and serum transfer-induced arthritis ameliorate these diseases but not in case of antigen-induced arthritis. TNF production and IL-17 responses were decreased in these models. These data shows that IL-38 could have anti-inflammatory properties in rheumatoid arthritis and probably could be use in a therapeutic strategy.[19]