Serum Th1/Th2 and Macrophage Lineage Cytokines in Leprosy; Correlation with Circulating CD4(+) CD25(high) FoxP3(+) T-regs Cells.

BACKGROUND: Not only macrophages, T-helper(Th)1 and Th2, but also CD4(+) CD25(high) FoxP3(+) regulatory T-cells(T-regs), are involved in immune response to Mycobacterium leprae.

OBJECTIVE: to evaluate serum interleukin(IL)-1β and IL-12p70(macrophage cytokines), interferon-γ(IFN-γ)(Th1 cytokine), IL-4(Th2 cytokine), and circulating CD4(+) CD25(high) FoxP3(+) T-regs, in untreated leprosy patients.

METHODS: 43 patients and 40 controls were assessed for the mentioned cytokines using ELISA. Patients were assessed for circulating T-regs using flow cytometry. Patients were subgrouped into tuberculoid(TT), pure neural leprosy(PNL), borderline cases, lepromatous(LL), type1 reactional leprosy(RL1), and erythema nodosum leprosum(ENL).

RESULTS: Serum IL-12p70, IFN-γ and IL-4 were significantly higher in patients versus controls(p<0.05). Serum IL-4 was highest in LL and lowest in RL1(p=0.003). Serum IL-1β levels was significantly higher in multibacillary versus paucibacillary patients(p=0.006). Significantly higher T-regs levels was detected in TT, RL1 and PNL, while the lowest levels in ENL(p<0.001), with significant differences versus controls(p<0.05). FoxP3 expression% was significantly lower in PNL than other patients and controls(p<0.05). T-regs/T-effs was lowest in ENL(p<0.05). IFN-γ correlated positively with T-regs but negatively with IL-1β(p=0.041&0.046 respectively), which correlated positively with Teffs%(p=0.05). IL-4 correlated positively with TregsFoxP3 expression%(p=0.009).

CONCLUSIONS: Circulating T-regs were increased in TT, RL1 and PNL patients, known of relatively high cell mediated immunity. This finding was supported by low FoxP3 expression(in PNL) and correlation between Tregs count and IFN-γ level. Overproduction of IL-4 in LL may infer liability to develop ENL, with disease progression and immune hyperactivation, marked by deficient T-regs and increased TregsFoxP3 expression%. IL-1β probably has a pro-inflammatory role in multibacillary patients as correlated with Teffs%. This article is protected by copyright. All rights reserved.