The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism.
BACKGROUND
Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism.


METHODS
Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA:


RESULTS
When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-gamma within the CD8(+) population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-alpha or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1beta and tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an increase of bone turnover in old age.


CONCLUSIONS
Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-gamma and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-alpha in monocytes) these changes are gender specific.
Department of Pathophysiology, University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria. peter.pietschmann@akh-wien.ac.at
Peter
P
Pietschmann
Eva
E
Gollob
Susanne
S
Brosch
Philipp
P
Hahn
Stephan
S
Kudlacek
Martin
M
Willheim
Wolfgang
W
Woloszczuk
Meinrad
M
Peterlik
Karl Heinz
KH
Tragl
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology; D012727:Sex Characteristics; D013601:T-Lymphocytes / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D012739:Gonadal Steroid Hormones; D006728:Hormones