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Cytokine production ex vivo: effect of raised body temperature
M Kappel1, N Tvede, M B Hansen
1Department of Infectious, National University Hospital, Copenhagen, Denmark.
Insights
This study found that human hyperthermia does not affect cytokine production by blood mononuclear cells (BMNC). However, indomethacin enhanced tumor necrosis factor-beta (TNF-beta) and interferon-gamma (IFN-gamma) production, suggesting altered prostaglandin sensitivity.
Area of Science:
- Immunology
- Human Physiology
Background:
- Cytokine production by blood mononuclear cells (BMNC) is crucial for immune responses.
- Hyperthermia, or elevated body temperature, can modulate immune function.
- The role of hyperthermia on cytokine profiles and the influence of prostaglandin synthesis inhibitors require further investigation.
Purpose of the Study:
- To investigate the impact of induced hyperthermia on the production of key cytokines: interleukin-1 alpha (IL-1α), IL-1 beta (IL-1β), tumor necrosis factor-beta (TNF-β), and interferon-gamma (IFN-γ).
- To determine the effect of indomethacin, a prostaglandin synthesis inhibitor, on these cytokine productions under both hyperthermic and thermoneutral conditions.
- To explore potential alterations in BMNC sensitivity to prostaglandins induced by hyperthermia.
Main Methods:
- Eight healthy volunteers underwent controlled hyperthermia (rectal temperature 39.5°C) via hot water immersion and a thermoneutral control condition.
- Blood samples were collected at various time points before, during, and after immersion.
- In vitro stimulation of BMNC with lipopolysaccharide or phytohemagglutinin was performed, with and without indomethacin, to measure cytokine levels in supernatants.
Main Results:
- Induced hyperthermia did not significantly alter the production of IL-1α, IL-1β, TNF-β, or IFN-γ from stimulated BMNC.
- Indomethacin significantly enhanced ex vivo TNF-β production under both hyperthermic and thermoneutral conditions.
- Indomethacin also augmented IFN-γ production, with no significant difference between hyperthermic and thermoneutral states.
Conclusions:
- Human hyperthermia does not directly inhibit or enhance the production of major cytokines by stimulated BMNC.
- Indomethacin's augmentation of TNF-β and IFN-γ suggests that prostaglandin pathways play a role in regulating these cytokines.
- The observed decline in indomethacin-enhanced TNF-β production during hyperthermia compared to controls indicates that hyperthermia may alter BMNC sensitivity to prostaglandins.
Abstract:
This study was designed to examine the effects of hyperthermia in humans on the production of interleukin (IL)-1 alpha, IL-1 beta, tumour necrosis factor (TNF)beta and interferon (IFN)gamma, determined in supernatants from in vitro lipopolysaccharide or phytohemagglutinin stimulated blood mononuclear cells (BMNC), including the effect of indomethacin in the assays on these cytokines. Eight healthy volunteers were immersed into a hot water bath (water temperature 39.5 degrees C) for 2 h, during which their rectal temperature rose to 39.5 degrees C. On a later day they served as their own controls, being immersed into thermoneutral water (34.5 degrees C) for 2 h. Blood samples were collected before, at body temperatures of 38, 39 and 39.5 degrees C, and 2 h after water immersion and at corresponding time points in the control experiment. Hyperthermia did not influence the production of cytokines from stimulated BMNC. Indomethacin in the assays significantly enhanced the ex vivo production of TNF beta at hyperthermic and thermoneutral conditions; this indomethacin enhanced production of TNF beta declined from pre-value in the hyperthermia experiment compared to the control experiment. Furthermore, indomethacin augmented the production of IFN gamma from stimulated BMNC both in the hyperthermic and the control experiments; the indomethacin effect was, however, not different at the two conditions. It is suggested that hyperthermia alters the sensitivity of BMNC to prostaglandins.