Effect of interferon-alpha-2a on the output of recirculating lymphocytes from single lymph nodes

The output of recirculating lymphocytes from cannulated popliteal lymph nodes in sheep was measured after administration of human recombinant interferon (rIFN)-alpha-2a. Interferon (IFN) injection caused a dramatic decrease in lymphocyte output from lymph nodes. Following a single s.c. or i.d. injection of 2 x 10(7) U IFN into the drainage area of the popliteal lymph node, lymphocyte output fell to below 1% of the pre-treatment level and remained depressed for up to 35 hr. A substantial decrease in lymphocyte output from cannulated nodes also occurred after IFN was injected either i.v., into the skin of the opposite non-cannulated hind leg or into an afferent lymphatic vessel leading to the popliteal lymph node. After the period of depressed lymphocyte output, a seemingly compensatory surge of cell traffic occurred that lasted 2-3 days. During this phase there was a relative increase in the proportion of CD4+ T cells in lymph. Similar changes occurred after each treatment in animals given multiple doses of IFN. These effects are unlikely to be antigen-induced since there was no blast cell response in any treated animal. The analysis of blood and lymph plasma samples showed that the most severe depression of lymphocyte output was associated with high levels of IFN, while there was no apparent correlation between the reduction in lymphocyte traffic and concentrations of cortisol in plasma. These results suggest that IFN-alpha-2a is involved directly in the regulation of lymphocyte output from lymph nodes.