Chronic administration of UK-114, a multifunctional emerging protein, modulates the Th1/Th2 cytokine pattern and experimental autoimmune diseases.

UK-114 is a 14-kDa ubiquitous protein recently sequenced by several groups throughout the world. Its activity ranges from being a tumor antigen, a protein synthesis inhibitor or a specific mu-calpain activator. UK-114 shows structural homologies also with proteins of the MHC-1 binding proteins, and heat shock proteins (HSPs). We investigated the possible effects of UK-114 on T helper cells cytokine profile and the development and progression of experimental autoimmune diseases. Homogeneous recombinant UK-114 was used in all experiments. Treatment of Balb/c male mice for two weeks resulted in the increase of IL-4, and the decrease of TNF-alpha, IFN-gamma, and IL-2 release from stimulated splenocytes, suggesting that UK-114 modulates the Th1/Th2 cytokine profile toward Th2. Similar to that observed with HSP60/65, a single pretreatment of Lewis rats with UK-114 significantly blunted the development of adjuvant-induced arthritis, whereas chronic treatment of 4-week-old female NOD mice dose dependently inhibited the development of diabetes.