VARIABLE EFFECTS OF PROOPIOMELANOCORTIN PEPTIDES ON THE PROLIFERATIVERESPONSE OF EQUINE IMMUNE CELLS

Large amounts of proopiomelanocortin (POMC) peptides may be secreted i n response to exercise training programs and various physical and psyc hological stressors. These peptides are also frequently released from hyperplastic pituitary tissues, pituitary adenomas and as part of the endogenous response to various infectious diseases. Work largely perfo rmed in other species indicates that the POMC peptides may have dramat ic effects on immunological function and related resistance to disease . The present study tested the effects of selected POMC peptide fragme nts on equine immune cells in order to gain a better understanding of related neuroimmunological interactions in the equine species. Periphe ral blood mononuclear cells (PBMCs) and peripheral T cells were collec ted from mature Thoroughbreds (n=6). Unconditioned animals were stalle d and samples collected between 7 and 9 AM. Quadruplicate wells of 2 X 10(5) cells were cultured with suboptimal phytohemagglutinin (PHA) in the presence or absence of 10(-5), 10(-7), 10(-9) and 10(-11) M hormo ne concentrations. Hormone treatments included synthetic adrenocortico tropic hormone (ACTH(I.39); A39/ACTH), camel-beta-endorphin (beta-E), alpha-melanocyte-stimulating hormone (alphaMSH), ACTH1.24 (Al), ACTH4. 10 (A4) and ACTH18-39 (A18). Hormone or vehicle and mitogen were added at the beginning of culture and the proliferative response was measur ed on day 3. Results were analyzed by ANOVA and means compared with LS D analysis. The proliferative response of PBMCs from geldings was redu ced (P<.05) by 10(-5) M A39/ACTH and A18 treatments. The 10(-9) M A39/ ACTH treatment stimulated (P<.01) proliferation of gelding PBMCs where as proliferation was not altered by A4 or Al fragments. The proliferat ive response of mare PBMCs was reduced (P<.01) by 10(-5) to 10(-9) M d osages of all truncated ACTH fragments and the 10(-5) M A39/ACTH treat ment. T cell proliferation was stimulated (P<.05) by all doses of alph aMSH and A4 as well as the 10(-7) M to 10(-9) M Al and the 10(-5) M be ta-E treatment. T cell proliferation was inhibited (P<.05) by 10(-5) M A39/ACTH treatments and there was no effect of the remaining treatmen ts. Results from this experiment indicate that POMC peptides and vario us ACTH fragments may function to regulate proliferation of equine imm une cells. The response of PBMCs may be mediated by distinct receptors since A18 extends outside of the core tetradecapeptide sequence norma lly associated with ACTH effects. Further, the response of equine immu ne cells to truncated ACTH fragments suggests that peptides released i n response to infection may act to coordinate the immunological respon se. Further work is needed to characterize the physiological significa nce of these effects.