CONTINUOUS ADMINISTRATION OF IL-13 TO MICE INDUCES EXTRAMEDULLARY HEMATOPOIESIS AND MONOCYTOSIS

IL-13, a recently identified Th2 cytokine, shares some, but not all, I L-4 functions, including inhibition of monocyte and macrophage activat ion, stimulation of human B cells, and induction of growth and differe ntiation of mouse bone marrow cells in vitro. We have now tested the i n vivo effects of recombinant mouse IL-13 (rIL-13) from stably transfe cted, high expressing BW5147 thymoma cells. After purification by anio n exchange chromatography, rIL-13 was administered in the peritoneal c avity of BALB/c mice via osmotic pump for 7 days. Spleens from the rIL -13-treated mice were significantly enlarged compared with control spl eens due to increased cellularity. In particular, increased numbers of immature erythroblasts and megakaryocytes were observed in splenic se ctions after rIL-13 treatment. Spleen cells from rIL-13-treated mice s howed greatly increased responsiveness in vitro to recombinant forms o f mouse IL-3, mouse granulocyte-macrophage CSF, or human CSF-1 and, to a lesser extent, to mouse IL-4 or IL-13. Moreover, the rIL-13-treated mice also showed significant increases in CFU-E, CFU-C, and erythroid burst colonies in the spleen, further indicating the presence of incr eased numbers of hemopoietic precursors. Hematologic analyses indicate d that rIL-13 treatment induced slight anemia and striking monocytosis . Finally, spleen cells from rIL-13-treated mice produced significantl y more IL-6 upon LPS stimulation. Interestingly, the strong Th2 respon se induced by Nippostrongylus brasiliensis infection was also accompan ied by an increase in hemopoietic precursor frequencies in the spleen. Collectively, these data indicate that exogenous rIL-13 induces extra medullary hemopoiesis in mice and suggest that endogenous IL-13 may co ntribute to replenishment of effector cells during strong Th2 response s.