Role of human neutrophil peptide-1 as a possible adjunct to antituberculosis chemotherapy.
We report the role of human neutrophil peptide (HNP)-1 as an adjunct to antituberculosis (anti-TB) drugs. The combination of HNP-1, isoniazid, and rifampicin was evaluated against Mycobacterium tuberculosis H(37)Rv in vitro, ex vivo, and in vivo, and synergism was observed on the basis of reductions in minimum inhibitory concentrations (MICs) of these agents. In vitro results revealed >1-log unit reductions even when HNP-1 and anti-TB drugs were used at 1/16 MICs. This combination was also found to be bactericidal against intracellular mycobacteria even at 1/8 MICs of HNP-1 and drugs. HNP-1 used in conjunction with anti-TB drugs resulted in significant clearance of bacterial load from lungs, liver, and spleen of infected, compared with control animals. The effective therapeutic dosage of drugs could be reduced to half by supplementing HNP-1 in the therapeutic schedule. These results clearly suggest that HNP-1 can be used as adjunct chemotherapy with conventional drugs against TB.
Kalita
Anjana
A
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Verma
Indu
I
Khuller
G K
GK
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D007538:Isoniazid / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D014376:Tuberculosis / Q000188:drug therapy*; D023084:alpha-Defensins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D000995:Antitubercular Agents; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D007538:Isoniazid; D012293:Rifampin