INTERLEUKIN-2-INDUCED ENHANCEMENT OF AN ANTIGEN-SPECIFIC IGM PLAQUE-FORMING CELL RESPONSE IS MEDIATED BY THE SYMPATHETIC NERVOUS-SYSTEM

Interleukin (IL)-2, a lymphokine produced by activated T-cells, stimul ates T-cell proliferation and differentiation and potentiates B-cell p roduction of antigen-specific immunoglobulins. IL-2 also increases hyp othalamic norepinephrine turnover without affecting plasma corticoster one levels, which suggests that it selectively impacts on central site s that mediate sympathetic outflow to lymphoid organs. Because sympath etic stimulation during the early phases of an immunoglobulin (Ig)M pl aque-forming cell (PFC) response to sheep red blood cells results in a n increase in the subsequent number of antibody-forming cells, we asse ssed whether the enhancing effects of IL-2 on the PFC response are med iated by the sympathetic nervous system. The peak splenic IgM PFC resp onse was increased in male Sprague-Dawley rats and BALB/c mice adminis tered recombinant human IL-2 (50, 100 or 200 ng i.p.) in close tempora l congruity with sheep red blood cell administration (i.e., 1 day befo re or immediately before immunization), compared with vehicle-treated controls. IL-2 administered at a later interval after immunization (i. e., 2 days) did not increase the number of antibody-forming cells. Int act sympathetic innervation of the spleen was required for the IL-2-in duced immunoenhancement to occur because cutting the splenic nerve 10 days prior to IL-2 administration blocked the lymphokine's potentiatio n of the IgM PFC response. The immunostimulatory effects of IL-2 were also blocked in mice administered the beta adrenergic antagonist propr anolol (5 mg/kg) immediately and 1 day after IL-2 administration. The alpha adrenergic antagonist phentolamine (5 mg/kg) had no effect. Henc e, IL-2-induced enhancement of the IgM PFC response is time-dependent, requires an intact splenic nerve and is selectively blocked by a beta adrenergic antagonist. It is suggested that the sympathetic nervous s ystem plays a fundamental role in mediating the potentiating effects o f a lymphokine on an antigen-specific IgM PFC response.