Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4(+) CD25(high) FoxP3(+) T-regs cells

Exp Dermatol. 2014 Oct;23(10):742-7. doi: 10.1111/exd.12529.

Abstract

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. We aimed 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. Forty three 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), type 1 reactional leprosy (RL1) and erythema nodosum leprosum (ENL). 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 T-effs%( P = 0.05). IL-4 correlated positively with T-regs FoxP3 expression% (P = 0.009). We concluded that: 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 T-regs 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 T-regs FoxP3 expression%. IL-1β probably has a pro-inflammatory role in multibacillary patients as correlated with T-effs%.

Keywords: T-regs; interferon-γ; interleukins; leprosy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cytokines / blood*
  • Female
  • Forkhead Transcription Factors / blood
  • Humans
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Interleukin-1beta / blood
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-4 / blood
  • Leprosy / blood
  • Leprosy / classification
  • Leprosy / immunology*
  • Macrophages / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / classification
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Young Adult

Substances

  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • IL4 protein, human
  • Interleukin-1beta
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma