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Release of interleukin-1 and interleukin-6 from human monocytes by
antithymocyte globulin: requirement for de novo synthesis
P Rameshwar and P Gascon
Department of Medicine, University of Medicine and Dentistry, New Jersey
Medical School, Newark 07103.
Antithymocyte globulin (ATG) is an effective treatment in patients with
severe aplastic anemia (SAA). Its mechanism of action remains unclear,
although it has been assumed to be immunosuppressive. However, ATG has also
been shown by several laboratories to be immunostimulatory. Recently,
interleukin-1 (IL-1) production has been found to be decreased in
lipopolysaccharide-stimulated peripheral blood monocytes obtained from SAA
patients. We have investigated the ability of ATG to function as an
immunostimulatory agent via the production of IL-1 and IL-6 by normal human
monocytes in vitro. Supernatants from ATG- stimulated monocytes were
assayed for biologically active and immunoreactive IL-1 and IL-6. We have
found that ATG, via its F(ab')2 fragment is a powerful inducer of IL-1 and
IL-6 production. Furthermore, ATG induction of both cytokines from normal
monocytes required de novo synthesis, as determined by 35S-methionine
incorporation. Because these two cytokines synergize with other cytokines
at both the stem cell and progenitor levels, these stimulatory properties
of ATG may be relevant to the treatment of SAA. This would favor the
hypothesis of a bimodal mechanism for ATG as an inducer of hematopoietic
growth factors and as an immunosuppressive agent.
Volume 80,
Issue 10,
pp. 2531-2538,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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