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, stimulates T-cell proliferation and differentiation and potentiates B-cell production of antigen-specific immunoglobulins. IL-2 also increases hypothalamic norepinephrine turnover without affecting plasma corticosterone levels, which suggests that it selectively impacts on central sites that mediate sympathetic outflow to lymphoid organs. Because sympathetic stimulation during the early phases of an immunoglobulin (Ig)M plaque-forming cell (PFC) response to sheep red blood cells results in an increase in the subsequent number of antibody-forming cells, we assessed whether the enhancing effects of IL-2 on the PFC response are mediated by the sympathetic nervous system. The peak splenic IgM PFC response was increased in male Sprague-Dawley rats and BALB/c mice administered recombinant human IL-2 (50, 100 or 200 ng i.p.) in close temporal congruity with sheep red blood cell administration (i.e., 1 day before 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. Intact sympathetic innervation of the spleen was required for the IL-2-induced immunoenhancement to occur because cutting the splenic nerve 10 days prior to IL-2 administration blocked the lymphokine's potentiation of the IgM PFC response. The immunostimulatory effects of IL-2 were also blocked in mice administered the beta adrenergic antagonist propranolol (5 mg/kg) immediately and 1 day after IL-2 administration. The alpha adrenergic antagonist phentolamine (5 mg/kg) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
S
S
Zalcman
J M
JM
Green-Johnson
L
L
Murray
W
W
Wan
D M
DM
Nance
A H
AH
Greenberg
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects*; D000941:Antigens / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*
D000941:Antigens; D007075:Immunoglobulin M; D007376:Interleukin-2; D011433:Propranolol; D010646:Phentolamine