S52 Poster Abstracts

AGE- AND SEX-STEROID-RELAI’CD CHANCES IN GLlJCOCORTlCOlD SINSITIVITY AS MEASURED HY DEXAMETHASONE-SUPPRESSED CYTOKINE PRODUCTION AT BASELINE AND AFTER PSYCt~OSO(‘I.AI. STRESS

Nicalas Rohlcdcr’, Rcnate I:ngcl. IIug~ttc M. Kudiclka. Dirk II Hellhammer d Clcmcns Klrschbaum

Center for Psychobiological and Psychowmatic Rcsenrcb. Univcrslty of rrler, Dlctrvzhstrafle IO-I I, 54290 ‘Trw, Germany,

c-mail: nic@fpp.uni-tricr.dc

Agmg IS associated with an wxeasc m vulncrabllity to chroruc inllammatory diseases and mfcctions, which may be related

to changes in hypothalamus-pituitary-adrenal (tIPA) nxls functioning at older age. Data from different laboratories suggest, that elderly individuals show clcvatrd levels of cortisol which could lead to enhanced immunosupprcssion. However, the effects of a given ylucocorticoid (GC) lcvcl largely dcpcnd on the scnsitwity of the respectwe target tissue for GCs. We thus

investigated the role of GC scnsitivitl of mononuclear cells wth respect to production of pro-inflammato~ cytokines in

elderly SubJccts and young controls under pa~chosowl strcsh. Since the decline of gonadal steroids with agmg seems to exert an effect on the praductlon ot pro-intlammatory cytokmcs as well. wc trcated one group of elderly men with testosterone.

IS healthy elderly men (67.27 + I 63 y’s,). 13 cldcrl\ men receivmg testosterone treatment (68.69 * 1.67 yrs.), and 12 healthy young men (25.25 * 0 79 yrs ) wcrc cxposcd to the “l’ricr Social Stress Test” (TSST) with repeated blood sampling before and after stress. (iC scnutivity \ras measured by dose-dcpcndant dcxamcthasonc (DEX) inhibition of LPS-stimulated

cytokmc tumor necrosis factor-alpha (TNF-a) and mtcrlcukm-6 (IL-h) production in whole blood. As an Index of CC sensitivity, the dose of DliX nccdcd to mducc 50% Inhibition of cytokinc production (IC,,,) was calculated for each dose-

response curve ‘The ‘TSST induced signdicant mcrcasc~ of cortisol I” all groups (p’.OOOl) wth a trend to higher responses in untreated

elderly sub,jccts. At basclinc. (iC scnutl>ity was higher III both groups of older men. While the younger subjects showed an increase in CC sensitlvit> after the ‘I SST. a decrcasc is found in untrcatcd elderly SubJccts. Intcrcstmgly. a live-day

testosterone treatment mduccs an mcrrasc m GC xnsiti\It) after psychowcial stress in healthy cldcrly subjects. Wc conclude, that at older age the GC scncitl\ity of peripheral mononuclear cells is altered, which in concert with higher

co~tisol levels may contrlbutc to the Incrcnsed vulnerability to chrontc mflammatory diseases and infections in later life

Furthermore, gonadal stcrolds sxm to plq a nxdiatmg role m the mteraction of IIPA ~YIF and immune system.

THE INFLUENCE OF DEXAMETHASONE ON CHANGES IN PERIPHERAL LYMPHOCYTES AFTER PSYCHOLOGICAL STRESS

Juergen Henmg* 6t Petra Netter

Department of Psychology. Umversity of Giessen. F R.G

Numerous studtes reveal that stress leads to changes in the distribution pattern of peripheral lymphocytes However. while the involvement and the effects of catecholamines had been demonstrated using beta-receptor blockade, less data are available to investigate the intluence of corticosteroids on changes in the number of lymphocyte subsets in humans after psychological stress.

The evening (ltlpm) prior to the main experiment subjects received a single dose of 1 jmg dexamethasone (DEX) or placebo (PLA), respectively. The following day subjects were exposed to a 5 min public speaking task (including an anticipation period of 10 minutes) or a non-stress condition, which took place about 18h after pretreatment, a delay which has been described to be sufficient to maintain HPA-axis suppression without affecting the number of CD3, CD19, CD4 and CD8 positive peripheral lymphocyte subsets.

Public speaking lead to highly significant changes in the number of white blood cells as well as m all of the relative and absolute counts of peripheral lymphocyte subsets (CD3, CD19, CDJ. CD8) Pretreatment of DEX results in suppressed cortisol levels throughout the whole experiment. Stress induced changes in total leukocytes and percentage of lymphocytes were only marginally intluenced by DEX. Moreover, stress induced changes in the percentage of CD3, CDlY, and CD8 positive cells were not altered by DEX while for CD4+ cells a reduction immediately after the talk was lower atler DEX. With respect to absolute cell counts it is remarkable that DEX reduced the redistribution of CD8 positive cells during recovetv and potentiates the stress induced mcreases in the number of CD4+ cells.

The data will be discussed wtth respect to the assumption that corticosterotds may play an important role in the down regulation of catecholamine mediated cell migration which fits the assumption of Selye concerning the role of corticosteroids in the counter shock phase.