Enhancement of IL-1, IL-2 production and IL-2 receptor generation in patients with acute rheumatic fever and active rheumatic heart disease; a prospective study

In a prospective study, patients with quiescent rheumatic heart disease (CRHD), streptococcal pharyngitis (SP) and healthy normal subjects produced comparable amounts of IL-1 and IL-2, but acute rheumatic fever (ARF) patients produced significantly elevated amounts of IL-1 and IL-2 at all intervals up to 48 weeks. In active rheumatic heart disease (ARHD), IL-1 activity returned to within normal range at 48 weeks, but IL-2 activity remained persistently elevated compared with CRHD, SP and healthy age- and sex-matched volunteers. CD4⁺ T lymphocytes were significantly increased in the peripheral blood of ARF and ARHD patients. The amount of IL-2 produced by ARF and ARHD patients correlated with the percentage of helper T lymphocytes (CD4⁺ cells) but not with the percentage of suppressor/cytotoxic T lymphocytes (CD8⁺ cells). Moreover, pre- and post-phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures from ARF and ARHD patients contained higher proportions of IL-2R⁺ (CD25⁺) cells than those from patients with SP, CRHD and normal individuals, which persisted up to 48 weeks. The percentage of CD25⁺ cells in both types of PBMC cultures directly correlated with the percentage of CD4⁺ cells and not with CD8⁺ cells in active rheumatic patients only. These findings indicate that the immune response in ARF and ARHD patients is skewed to produce activated helper T cells that release IL-2 drives the accumulation of more T helper cells. The result is an undamped helper T cell response in the peripheral blood of these patients.