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Modulation of cellular immune responses in mice with disseminated histoplasmosis by recombinant interleukin-2.

Abstract
Depression of the cellular immune responses in mice with disseminated histoplasmosis is associated with deficient production of interleukin-2 (IL-2) by splenocytes. Therefore, we examined whether a highly purified preparation of IL-2, recombinant human IL-2 (rIL-2), could modify the cellular immune responses in infected mice and whether this lymphokine could alter the severity of histoplasmosis in animals. Exogenous rIL-2, at concentrations of up to 1,000 U/ml, failed to augment the proliferative responses to concanavalin A by unfractionated splenocytes or splenic T cells from mice infected for 1 week. In addition, rIL-2 did not modulate the plaque-forming cell response to sheep erythrocytes by splenocytes from these same mice. However, at week 3, rIL-2 in concentrations ranging from 10 to 1,000 U/ml considerably augmented the proliferative response to concanavalin A and plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice. Kinetics studies demonstrated that rIL-2 exerted maximal immunoregulatory activity when added on day 0 or 1 to cultures of splenocytes. In vivo administration of rIL-2, 200 to 20,000 U/day, for 10 days to normal and 3-week-infected mice did not alter the proliferative activity of splenocytes to concanavalin A; 200,000 U of rIL-2 per day actually depressed the proliferative responses of splenocytes from normal and infected mice. In vivo, rIL-2 did not modify delayed-type hypersensitivity responses to sheep erythrocytes or to histoplasmin by normal and infected mice. Moreover, treatment with rIL-2 in vivo did not reduce the number of Histoplasma CFU in spleens of mice. Thus, despite the immunoenhancing effect of rIL-2 in vitro, this lymphokine failed to exert similar effects in vivo.
AuthorsG S Deepe Jr, C L Taylor, J E Harris, W E Bullock
JournalInfection and immunity (Infect Immun) Vol. 53 Issue 1 Pg. 6-12 (Jul 1986) ISSN: 0019-9567 [Print] United States
PMID3487507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Interleukin-2
  • Recombinant Proteins
Topics
  • Animals
  • Cells, Cultured
  • Histoplasma (immunology)
  • Histoplasmosis (immunology)
  • Hypersensitivity, Delayed (immunology)
  • Immunity, Cellular
  • Interleukin-2 (immunology)
  • Lymphocyte Activation
  • Mice
  • Recombinant Proteins (immunology)
  • Spleen (immunology, microbiology)
  • T-Lymphocytes (immunology)
  • Time Factors

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