There is growing evidence that pancreatic stellate cells (PSCs) produce cytokines and take part in the regulation of inflammatory processes in the pancreas. IL-15 inhibits apoptosis of various cell populations. This study was performed to investigate whether PSCs produce IL- 15 and thereby can affect lymphocytes. Primary PSCs were isolated from rat pancreas using density gradient centrifugation. The mRNA expression of IL-15 was demonstrated by RTPCR, the IL-15 protein was analysed by immunoblotting. Lymphocytes obtained from rat mesenterial lymph nodes (LnLy) were co-cultured with in vitro activated PSCs. Apoptosis has been quantified by the binding of Annexin V - FITC with a flow cytometer. Proliferation was monitored using ³H-thymidine incorporation. PSCs express two splice variants of IL-15. The protein was detectable only in cell lysates but not in the cell culture supernatant. Co-cultivation of lymphocytes with PSCs and IL-15 inhibited spontaneous lymphocyte apoptosis and this effect was reduced by an anti-IL-15 antibody. Lymphocytes induced vice versa the proliferation as well as the collagen production of PSCs. The inhibition of spontaneous lymphocyte apoptosis in co-cultures with PSCs was at least partially mediated by cell-bound IL-15. This effect and the stimulation of PSCs by lymphocytes may lead to a circulus vitiosus resulting in the persistence of inflammatory processes and the development of fibrosis during chronic pancreatitis.