Serum galactomannan and interleukin-6 dynamics using an Aspergillus fumigatus lung infection mouse model with high and low virulence clinical strains

Abstract

Invasive pulmonary aspergillosis (IPA) remains a serious disease with a high mortality rate. Although antifungal drugs such as azole, polyene, and echinocandin have been effective when evaluating fungal load and survival rate as indicators in mouse lung infection models, there are discrepancies between non-clinical and clinical efficacy, and drugs with higher therapeutic efficacy are needed. If clinical therapeutic effects can be predicted more accurately in non-clinical practice, drugs with higher clinical efficacy could be developed. We investigated the usefulness of galactomannan and certain cytokines for the pathology and treatment evaluation of IPA. We performed various evaluations using clinical isolates of Aspergillus fumigatus with different virulence (Lethal Dose 50) in a mouse lung infection model. Detection timing and amount of galactomannan and interleukin-6 in serum were closely related to virulence, indicating that the timing and amount of A. fumigatus dissemination from the lungs into the bloodstream are involved in virulence. As increases in galactomannan and interleukin-6 are also used as indicators for clinical diagnosis, they could become important indicators for establishing non-clinical IPA models to more accurately predict the clinical effect of antifungal drugs.