Effects of neutralising interleukin-6 on glucocorticoid-mediated adaptations to stress in rat skeletal muscle and liver

Wilson, Nathaniel W. (2005-12)

Thesis (MSc)--Stellenbosch University, 2005.

Thesis

ENGLISH ABSTRACT: This study (2 x 2 factor design) describes an investigation into the physiological interaction between the peripheral endocrine and cytokine systems after the organism has been exposed to psychological stress. An in vivo rodent model with two interventions was used: (1) mild psychological stress (immobilisation for 2 hours per day, for 4 days); (2) an antiinterleukin (IL)-6-antibody injection. Thirty-nine male Wi star rats were divided into 4 groups and given either the antibody (CA, control antibody) or stress (IP, immobilisation placebo), or both (IA, immobilisation antibody), or neither (CP, control placebo). Antibody and placebo (saline) were injected intraperitoneally. Differences between groups for the following parameters were determined in blood or metabolic tissues, viz. skeletal muscle and liver: 1) corticosterone concentrations, 2) glucocorticoid receptor (GR) binding capacity and 3) activities of metabolic enzymes, tyrosine aminotransferase (TAT) and glutamine synthetase (GS). Groups lP and lA showed a significant loss in body mass (CP vs. lP, p<O.01; CA vs. lA, p<O.001), indicating a main effect of stress. The corticosterone concentrations of only group lP were significantly elevated compared to that of group CP (CP vs. lP, p<O.01), again indicating a main effect of stress. All three intervention groups (CA, lP, lA) had decreased GR binding capacity, with group lA showing a statistically greater decrease (CP vs. CA, p<O.05; IP vs. IA, p<O.01; CP vs. IP, p<O.001; CA vs. IA, p<O.001), indicating main effects of stress and antibody treatment. In groups IP and IA increased activities of both enzymes (TAT and GS) were measured (main effect of stress), with IA again showing the greatest statistically significant increase for both enzymes. The liver tissue displayed greater sensitivity to the stress and antibody regimes. This study provides the first conclusive in vivo evidence for IL-6 modulation of glucocorticoid action in peripheral tissues in response to mild psychological stress.

AFRIKAANSE OPSOMMING: Hierdie studie (met 'n 2 X 2 faktorontwerp) beskryf 'n ondersoek oor die fisiologiese interaksie tussen die perifere endokrien- en sitokiensisteme in organismes blootgestel aan psigologiese stres. Daar word gebruik gemaak van 'n in vivo-rotmodel met twee intervensies: (1) matige psigologiese stres (immobilisering vir 2 uur per dag vir 4 dae); (2) 'n anti-interleukin (IL)-6-antiliggaam inspuiting. Nege-en-dertig manlike Wistar rotte is in vier groepe verdeel en het óf antiliggaam (CA, antiliggaam kontrole), óf stres (IP, immobilisasie placebo), óf beide stres en antiliggaam (lA, immobilisasie antiliggaam) of geen behandeling ontvang (CP, placebo kontrole). Die antiliggaam- en placebo (soutoplossing)- inspuitings is intraperitoneaal toegedien. Verskille tussen die groepe van die volgende parameters, in metaboliese weefsels (skeletspier en lewer), was bepaal: 1) kortikosteroon konsentrasies, 2) glukokortikoïed reseptor (GR) bindingskapasiteit en 3) aktiwiteite van die metaboliese ensieme, tirosien aminotransferase (TAT) en glutamien sintetase (GS). Groepe IP en IA het 'n beduidende afname in gewig getoon (CP vs. IP, p<O.01;CA vs. IA, p<O.001), wat 'n hoof-effek van stres aandui. Die kortikosteroon konsentrasies van slegs IP het beduidend toegeneem in vergelyking met CP (CP vs. IP, p<O.01),wat weereens 'n hoof-effek van stres aandui. AI drie intervensiegroepe (CA, IP, IA) het verlaagte GR bindingskapasiteit getoon, met lA wat 'n groot statistiese afname getoon het (CP vs. CA, p<O.05; IP vs. IA, p<O.01;CP vs. IP, p<O.001;CA vs. IA, p<O.001),wat hoof-effekte van beide stres en antiliggaam-behandeling aandui. In groepe IP and IA is toenames in beide ensiemaktiwiteitvlakke (TAT en GS ensieme) getoon (hoof-effek van stres), met IA wat weereens die grootste toename gewys het. Die lewer het ook verhoogde sensitiwiteit tot die stres- en antiliggaamregimente. Hierdie studie lewer die eerste daadwerklike in vivo bewyse vir IL-6 modulering van glukokortikoïedaksie in perifere weefsels na reaksie op psigologiese stres.

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