Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6.
Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.
Smith
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C
Department of Physiological Sciences, University of Stellenbosch, Private Bag X1, Matieland 7602, South Africa. csmith@sun.ac.za
Wilson
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NW
Louw
A
A
Myburgh
K H
KH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood; D015536:Down-Regulation / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000032:analysis / Q000378:metabolism; D007103:Immobilization / Q000523:psychology*; D053583:Interleukin-1beta / Q000097:blood / Q000502:physiology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology; D014444:Tyrosine Transaminase / Q000032:analysis / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000906:Antibodies; D003345:Corticosterone; D005974:Glutamate-Ammonia Ligase; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D014444:Tyrosine Transaminase; D000093242:Interleukin-6 Inhibitors