title: Serum Th1/Th2 and macrophage lineage cytokines in leprosy; correlation with circulating CD4(+) CD25(high) FoxP3(+) T-regs cells.
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%.
authors.affiliation: Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: Abdallah
authors.forename: Enas A S
authors.initials: EA
authors.lastname: Attia
authors.forename: Abeer A
authors.initials: AA
authors.lastname: Saad
authors.forename: Ekramy A
authors.initials: EA
authors.lastname: El-Khateeb
authors.forename: Rania A
authors.initials: RA
authors.lastname: Lotfi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abdallah
authors.forename: Dina
authors.initials: D
authors.lastname: El-Shennawy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood*; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D007918:Leprosy / Q000097:blood / Q000145:classification / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; C508598:IL4 protein, human; D053583:Interleukin-1beta; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: T-regs; interferon-γ; interleukins; leprosy