The serum level of the immunomodulatory peptide cathelicidin LL37 and T helper cell type 1 inflammatory response in viral hepatitis B, C, and D

Abstract Cathelicidin LL37 is an innate immunity antimicrobial peptide involved in the immune modulation of IFN-Abstract Cathelicidin LL37 is an innate immunity antimicrobial peptide involved in the immune modulation of IFN-γ, the key cytokine of T helper cell type 1 (Th1) response. The role of LL37 in viral hepatitis inflammation is unknown. We assessed the serum variations of LL37 and the Th1 response in hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. The LL37 level (Elisa detection) and Th1 response (defined by IFN-γ level, CD4+ and CD8+ T cell count) were analyzed in 87 patients: 65 hepatitis patients (34 HCV, 18 HBV, 13 HDV) and 22 healthy controls. The subjects, 33 males/ 54 women aged 20-64 years, were selected at "Matei Bals" Institut, Bucharest, Romania. Hepatitis patients were classified according to viral etiology and viral replication as active cases (detectable viremia) versus negative cases (undetectable viremia). Student T test and Mann Whitney analysis were applied. High levels of LL37 (138.09±88.45ng/ml, p=0.045) and IFN-γ (69.82 pg/ml, p=0.005) were detected in the whole group of hepatitis. Active HCV hepatitis presented a significant increase in LL37 level (155.15±78.84ng/ml, p=0.014) and Th1 response by comparison with inactive HCV hepatitis. Conversely active HBV patients displayed low LL37 levels (76.75ng/ml, p=0.009) and no Th1 dominant response by comparison with inactive B hepatitis. High levels of LL37 up to 171.01±72.08 ng/ml and a moderate Th1 response defined HDV patients. Our results highlights increased levels of the cathelicidin LL37 in all viral hepatitis correlated with a strong and concordant immune response in active HCV hepatitis. , the key cytokine of T helper cell type 1 (Th1) response. The role of LL37 in viral hepatitis inflammation is unknown. We assessed the serum variations of LL37 and the Th1 response in hepatitis C virus (HCV), hepatitis B virus (HBV) and hepatitis D virus (HDV) infections. The LL37 level (Elisa detection) and Th1 response (defined by IFN-γ level, CD4+ and CD8+ T cell count) were analyzed in 87 patients: 65 hepatitis patients (34 HCV, 18 HBV, 13 HDV) and 22 healthy controls. The subjects, 33 males/ 54 women aged 20-64 years, were selected at "Matei Bals" Institut, Bucharest, Romania. Hepatitis patients were classified according to viral etiology and viral replication as active cases (detectable viremia) versus negative cases (undetectable viremia). Student T test and Mann Whitney analysis were applied. High levels of LL37 (138.09±88.45ng/ml, p=0.045) and IFN-γ (69.82 pg/ml, p=0.005) were detected in the whole group of hepatitis. Active HCV hepatitis presented a significant increase in LL37 level (155.15±78.84ng/ml, p=0.014) and Th1 response by comparison with inactive HCV hepatitis. Conversely active HBV patients displayed low LL37 levels (76.75ng/ml, p=0.009) and no Th1 dominant response by comparison with inactive B hepatitis. High levels of LL37 up to 171.01±72.08 ng/ml and a moderate Th1 response defined HDV patients. Our results highlights increased levels of the cathelicidin LL37 in all viral hepatitis correlated with a strong and concordant immune response in active HCV hepatitis. Rezumat Cathelicidina LL37 este un peptid antimicrobicin aparţinând imunităţii înnăscute, implicat în modularea IFN-y, citokina cheie a răspunsului T helper de tip 1. Rolul LL37 în răspunsul inflamator din cursul hepatitelor virale este necunoscut\ Am evaluat variaţiile serice ale LL37 şi răspunsul Thl în infecţiile cu virus hepatitic C (HCV), cu virus hepatitis B (HBV) şi cu virus hepatitic D (HDV). Nivelul LL37 (analizat prin test ELISA) şi răs- punsul Thl (definit prin nivelul IFN-y şi numărul de celule CD4+ şi CD8+) au fost analizate la 87 pacienţi (65 cu hepatită (34 HCV, 18 HBV, 13 HDV) şi 22 martori sănătoşi. Subiecţii, 33 bărbaţi/54 femei, între 20-64 ani, au fost selectaţi la Institutul Matei Balş, Bucureşti, România, în septembrie 2011 -martie 2012. Pacienţii cu he- patită au fost analizaţi în funcţie de etiologie şi de activitatea virală (activi vs inactivi). S-a folosit testul t student şi Mann Whitney. In grupul total de hepatite au fost detectate nivele ridicate de LL37 (138,09±88,45ng/ml, p=0,045) şi IFN-y (69,82pg/ml, p=0,005). în hepatita C activă nivelul de LL37 a fost semnificativ crescut (155,15±78,84ng/ml, p=0,014) şi răspunsul Thl a fost predominant în raport cu forma inactivă. Dimpotrivă, pa- cienţii cu hepatită B activă au prezentat LL37 scăzut (76,75ng/ml, p=0,009), fără răspuns Thl dominant compa- rativ cu forma inactivă. în hepatita D s-au întâlnit nivele de LL37 crescute până la 171,01 ±72,08ng/ml şi un răs- puns moderat Thl. Rezultatele indică un răspuns imun puternic şi concordant în hepatita C activă şi nivele cres- cute de LL37 în toate hepatitele virale.