Effects of interleukin-2 on the expression of corticotropin-releasing hormone in nerves and lymphoid cells in secondary lymphoid organs from the Fischer 344 rat

This study examined the influence of interleukin (IL)-2 on corticotropin releasing hormone (CRH) immunoreactivity in the Fischer 344 (F344) rat spleen. Rats were given either vehicle or 1, 10, 25, 50, 100, or 200 ng of human recombinant (hr)IL-2 by intraperitoneal (i.p.) injection, and were sacrificed 0.5, 1, 4, 12, or 24 h after treatment. Spleens and mesenteric lymph nodes were prepared for immunocytochemistry to localize CRH. In spleens from vehicle-treated animals, CRH immunoreactivity was present in several types of cells of the immune system, but CRH⁺ nerves were not observed in either spleens or lymph nodes from vehicle-treated animals. Treatment with IL-2 induced CRH expression in nerves in the spleen in a dose- and time-dependent manner. CRH⁺ nerves were not found in the mesenteric lymph nodes after IL-2 treatment, instead a dramatic time- and dose-dependent accumulation of CRH⁺ cells (resembling small lymphocytes and large granular mononuclear cells) in the cortex and medulla. These findings indicate that IL-2 stimulates the synthesis of CRH in nerves that innervate the F344 rat spleen, and promote the appearance of CRH⁺ immunocytes into draining mesenteric lymph nodes.