Effect of amphotericin B lipid formulation on immune response in aspergillosis.
The immune response against Aspergillus fumigatus has been studied during infection and therapy in order to understand the mechanism of pathogenesis and the effect of treatment with amphotericin B. With this in view an animal model of aspergillosis was developed in Balb/c mice by intravenous injection of an optimized dose of 3. 6x10(6) A. fumigatus spores. Infection due to Aspergillus was well established by histopathological examination and fungal load in the animal. Lesions and eosinophil infiltration was observed in the infected tissues which indicated the involvement of a Type I hypersensitivity response. Evaluation of serological parameters indicated high levels of interleukin-4 (IL-4) and A. fumigatus specific IgG antibodies. The reduction in fungal load and modulation of immune response in the infected mice was studied following treatment with amphotericin B/cholesterol hemisuccinate vesicles (ABCV). The results clearly indicated significant reduction in the fungal load, disappearance of eosinophils and lesions with the appearance of macrophages and neutrophils in the infected lung tissue, a decrease in IL-4 (fourfold) and a concomitant increase of interferon-gamma (IFN-gamma; twofold) with an improvement in general condition of mice. In the non-treated mice, the rise of IL-4 level indicated the association of T(H)2 cell response with susceptibility to infection while the increase of IFN-gamma in the treated group suggested that T(H)1 cell response may be involved in resistance to Aspergillus infection.
Saxena
S
S
Department of Biochemistry, University of Delhi South Campus, Benito Juarez Road, New Delhi, India.
Bhatnagar
P K
PK
Ghosh
P C
PC
Sarma
P U
PU
D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood / Q000187:drug effects*; D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus / Q000187:drug effects* / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage / Q000737:chemistry; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004339:Drug Compounding; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D016019:Survival Analysis; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000908:Antibodies, Fungal; D000935:Antifungal Agents; D016207:Cytokines; D007074:Immunoglobulin G; D000666:Amphotericin B; D002784:Cholesterol