Mediation of the immunomodulatory effect of beta-estradiol on inflammatory responses by inhibition of recruitment and activation of inflammatory cells and their gene expression of TNF-alpha and IFN-gamma.

Abstract

BACKGROUND:

Estrogen has long been reported to show immunomodulatory effects on immune responses, yet, its specific anti-inflammatory mechanism is not clear.

METHODS:

In this study, we analyzed the effects of beta-estradiol (E2), at its contraceptive dose, on both T cell-independent and T cell-dependent inflammations, and the associated immune mechanism, in female mice. The T cell-independent inflammation was locally induced either with an intradermal injection of olive oil in the footpad, or by an intraperitoneal injection of proteose peptone (PP). The T cell-dependent inflammation was induced by an intraperitoneal injection of the purified protein derivatives (PPD).

RESULTS:

While E2 inhibited olive oil-induced inflammation as monitored by the decrease in footpad swelling, it did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by cells at the inflammatory locus. E2 also inhibited PP-induced inflammation as monitored by the decrease in the number of inflammatory peritoneal exudate cells (PEC) coinciding with a marked decrease in the number of macrophages and granulocytes (Gr. 1+). While E2 did not affect the gene expression of monocyte chemoattractant protein-1 and IL-6 by PP-elicited PEC, it decreased both gene expression and production of TNF-alpha. E2 also decreased the number of cells expressing the lymphocyte function-activated protein-1 in PP-elicited PEC, but not for CD62L. In purified protein derivative-induced T cell-dependent inflammation, E2 decreased the total cellularity of PEC and the relative numbers of CD3+ and CD4+ T cells, and the number of cells expressing the lymphocyte activation markers CD40, CD44, CD69 and IL-2Ralpha in PEC. Furthermore, while E2 did not affect the gene expression of the early T lymphocyte activation protein-1 by PEC, it decreased the gene expression of INF-gamma.

CONCLUSION:

Collectively, the results suggest that E2-mediated inhibition of inflammatory responses may be due to a combination of suppression of homing and activation of inflammatory cells and their production of TNF-alpha and IFN-gamma.

• Authors: M L Salem, M S Hossain, K Nomoto
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 121 Issue 3 Pg. 235-45 (Mar 2000) ISSN: 1018-2438 [Print] Switzerland
• PMID: 10729783 (Publication Type: Journal Article)
• Copyright: Copyright 2000 S. Karger AG, Basel

Chemical References

• Adjuvants, Immunologic
• Caseins
• Chemokine CCL2
• Chemokines
• Cytokines
• Interleukin-6
• Olive Oil
• Peptide Fragments
• Plant Oils
• Tumor Necrosis Factor-alpha
• proteose-peptone
• Estradiol
• Interferon-gamma

Topics

• Adjuvants, Immunologic (administration & dosage)
• Animals
• Caseins (toxicity)
• Cell Movement (immunology)
• Chemokine CCL2 (genetics)
• Chemokines (biosynthesis, genetics)
• Cytokines (biosynthesis, genetics)
• Edema (chemically induced, immunology, pathology)
• Estradiol (administration & dosage)
• Female
• Foot (pathology)
• Gene Expression Regulation (immunology)
• Inflammation (chemically induced, immunology, pathology)
• Injections, Intradermal
• Interferon-gamma (genetics)
• Interleukin-6 (genetics)
• Macrophage Activation
• Macrophages, Peritoneal (immunology, pathology)
• Mice
• Mice, Inbred C3H
• Olive Oil
• Peptide Fragments (toxicity)
• Plant Oils (toxicity)
• Tumor Necrosis Factor-alpha (genetics)