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Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages

W J Fraser¹, Z Haffejee, D Jankelow

¹Department of Anatomical Pathology, School of Pathology, South African Institute for Medical Research, Johannesburg, South Africa.

|January 7, 1998

Summary

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Macrophages initiate rheumatic fever inflammation by secreting interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), preceding lymphocyte involvement. Interleukin-2 (IL-2) appears later, supporting proposed developmental stages of Aschoff nodules.

Area of Science:

Rheumatic heart disease pathogenesis
Immunohistochemistry of inflammatory lesions
Cytokine signaling in autoimmune disease

Background:

Aschoff nodules are characteristic lesions in rheumatic fever.
Previous studies proposed three developmental stages based on lymphocyte infiltration.
The role of specific cytokines in these stages was not fully understood.

Purpose of the Study:

To investigate the distribution and role of IL-1, IL-2, and TNF-α in different stages of Aschoff nodules.
To test the hypothesis that macrophages precede lymphocytes in Aschoff nodule development.

Main Methods:

Immunohistochemistry was performed on 14 rheumatic fever valve specimens.
Lesions were staged based on lymphocyte presence (macrophages only, few T lymphocytes, many B and T lymphocytes).

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Expression of IL-1, IL-2, TNF-α, CD4, and CD8 was analyzed.

Main Results:

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) were expressed by macrophages in stage 1 and 2 lesions.
Stage 3 lesions showed variable expression of IL-1, TNF-α, and IL-2, with IL-2 found in lymphoid aggregates.
T lymphocytes (CD4 and CD8 positive) were phenotyped.

Conclusions:

Macrophage secretion of TNF-α and IL-1 is crucial for lymphocyte activation and aggregation, indicating macrophages initiate the inflammatory response.
Interleukin-2 (IL-2) expression occurs later, primarily within lymphoid aggregates.
Findings support the proposed sequential developmental stages of Aschoff nodules.