Splenic lymphocyte production of an endorphin during endotoxic shock.
Endogenous opioids have been reported to elicit some of the pathophysiologic responses to endotoxic shock by binding to the delta-opiate receptor. We have previously reported the production of immunoreactive (ir)-endorphin by B lymphocytes treated with bacterial lipopolysaccharide (LPS). We postulated that this lymphocyte-derived ir-endorphin may be an extrapituitary source of the endogenous opioid component associated with the pathophysiology of endotoxic shock. To test this hypothesis, we chose to study the LPS-sensitive (C3HeB/FeJ) and -resistant (C3H/HeJ) inbred mouse model. We treated these mice with intraperitoneal injections of LPS or B-lymphocyte-derived ir-endorphin. The LPS-sensitive mice presented with a severe hypothermic and pathophysiologic response pattern when treated with LPS or with ir-endorphin. The LPS-resistant mice, which were unresponsive to the LPS, however, presented with the typical hypothermic and pathophysiologic responses to the ir-endorphin. Immunofluorescence on the splenic leukocytes in the LPS-treated mice showed significant ir-endorphin present only in the LPS-sensitive mice at a time point preceding onset of the pathophysiologic response pattern. Taken together, this evidence strongly suggests a role for B-lymphocyte-derived ir-endorphin in the pathophysiology of endotoxic shock. The implications of immune system regulation of neuroendocrine function are discussed.
Harbour
D V
DV
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Smith
E M
EM
Blalock
J E
JE
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D004351:Drug Resistance; D005455:Fluorescent Antibody Technique; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008809:Mice, Inbred C3H; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D013154:Spleen / Q000166:cytology* / Q000378:metabolism
D008070:Lipopolysaccharides; D011333:Pro-Opiomelanocortin