Cytokine production and lymphocyte transformation during stress

doi:10.1016/0889-1591(91)90029-A

Brain, Behavior, and Immunity

Volume 5, Issue 4, December 1991, Pages 339-348

https://doi.org/10.1016/0889-1591(91)90029-A Get rights and content

Abstract

The production of interleukin-1β (IL-1β) and interferon-γ (IFNγ) and blast transformation in peripheral blood mononuclear cells were assessed in medical students writing an academic examination. Blood samples were obtained on three occasions: (1) 1 month prior to the examination during a period of relatively low academic demand; (2) immediately after the examination; and (3) 10 days later. Results indicated that immune responses were significantly different immediately after the examination compared with the baseline and postexam measures. Lymphocyte responsiveness to both concanavalin A and pokeweed mitogen was decreased, as was the production of IFN_γ, supporting earlier reports of immunosuppression after relatively commonplace stressors. In contrast to predictions, IL-1β production was significantly elevated after the examination. Cortisol levels were also measured, but did not change across the three sample points. Our finding of an increase in IL-1β production suggests that stress may have different effects on different cell populations by enhancing the responses of monocytes and depressing those of lymphocytes.

References (29)

R.W. Bartrop et al.
Depressed lymphocyte function after bereavement
Lancet
(1977)
R. Glaser et al.
Stress-related immune suppression: Health implications
Brain, Behav. Immun
(1987)
J. Palmblad et al.
Stressor exposure and immunological response in man: Interferon-producing capacity and phagocytosis
J. Psychosom. Res
(1976)
P.I.M. Allen et al.
Dissociation between emotional and endocine responses preceding an academic examination in male medical students
J. Endocrinol
(1985)
A. Boyum
Separation of leukocytes from blood and bone marrow
Scan. J. Clin. Lab. Invest
(1968)
C.A. Dinarello
Biology of Interleukin-1
FASEB J
(1988)
B. Dorian et al.
Aberations in lymphocyte subpopulations and functions during psychological stress
Clin. Exp. Immunol
(1982)
M.L. Drakes et al.
Effects of gold on the production and response to human interleukin-1
J. Rheumatol
(1987)
G.W. Firestein et al.
How important are T cells in chronic rheumatoid synovitis?
Arthritis Rheum
(1990)
M. Gibaldi et al.
Pharmacokinetics
(1982)

R. Glaser et al.

Stress, loneliness, and changes in herpesvirus latency

J. Behav. Med

(1985)

R. Glaser et al.

Stress depresses interferon production and natural killer cell activity in humans

Behav. Neurosci

(1986)

A. Gorbman et al.

Comparative Endocrinology

(1983)

M. Harth et al.

The modulation of interleukin-1 production by interferon-γ and the inhibitory effects of gold compounds

Immunopharmacology

(1990)

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¹: This research was supported by a Medical Research Council Studentship to J.P.D., and by a grant from the University Hospital Foundation.

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Cytokine production and lymphocyte transformation during stress

Abstract

Lancet

Brain, Behav. Immun

J. Psychosom. Res

Dissociation between emotional and endocine responses preceding an academic examination in male medical students

J. Endocrinol

Separation of leukocytes from blood and bone marrow

Scan. J. Clin. Lab. Invest

Biology of Interleukin-1

FASEB J

Aberations in lymphocyte subpopulations and functions during psychological stress

Clin. Exp. Immunol

Effects of gold on the production and response to human interleukin-1

J. Rheumatol

How important are T cells in chronic rheumatoid synovitis?

Arthritis Rheum

Pharmacokinetics