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Toxicologic Pathology
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Journal Article

Interleukin 1 and Interferon-{gamma}: Cytokines that Provide Reciprocal Regulation of Macrophage and T Cell Function

Richard M. Schultz

Department of Immunology Research, Lilly Research Laboratories, Indianapolis, Indiana 46285

Interactions between macrophages and T cells are symbiotic, since optimal functions of both cell types require interchange of soluble mediators. Upon activation, macrophages release interleukin-1 (alias lymphocyte activating factor, leukocytic endogenous mediator, and endogenous pyrogen), a family of molecules with multivarious biological effects, ranging from induction of fever and the acute phase response to lymphocyte activation and concomitant release of interleukin-2. Interleukin-2 induces activation and replication of several subsets of precursor lymphocytes, including cytotoxic T cells, lymphokine-activated killer (LAK) cells, and natural killer (NK) cells, and enhances their cytotoxic activity for tumor cells. Both interleukin-2 and leukotrienes enhance production of immune interferon (interferon-{gamma}) by activated T cells. Aside from antiviral activity, interferon-{gamma} produces a number of immunomodulatory effects, including macrophage activation (Ia induction, antimicrobial effector function, and activation of oxidative metabolism) and augmentation of NK function. Expression of Ia on accessory cell membranes is required for the initiation of many antigen-specific, T-dependent immune responses. Interferon-{gamma} also synergizes with a variety of microbial agents to augment macrophage tumoricidal function and enhance interleukin-1 secretion. The production of interferon-{gamma} appears to have a critical role in feeding back the cascade of interleukins in a loop of amplification. Both interleukin-1 and interferon-{gamma} modulate release of arachidonate metabolites in various cells. This cascade of cytokines, in collaboration with arachidonate oxygenation products, regulates immunity and sets the stage for many of the events underlying inflammation. Various anti-inflammatory drugs and immunopotentiators appear to act by modulating cytokine pathways.

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Toxicologic Pathology, Vol. 15, No. 3, 333-337 (1987)
DOI: 10.1177/019262338701500311
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This Article
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