losartan-potassium and Histoplasmosis

Topics: Acquired Immunodeficiency Syndrome; Amphotericin B; Anemia; Erythropoietin; Histoplasmosis; Humans; Recombinant Proteins; Zidovudine

Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80(+)/CD80(+) and F4/80(+)/CD86(+) cells to the bronchoalveolar space, induced higher production of IFN-γ, IL-6, MIP-1α, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection.

Topics: Animals; Apoptosis; Bronchoalveolar Lavage Fluid; Chemokine CCL2; Chemokine CCL3; Chemokines; Erythropoietin; Gene Expression Regulation; Histoplasma; Histoplasmosis; Inflammation; Interferon-gamma; Interleukin-6; Lung; Macrophages; Male; Mice; Mice, Inbred C57BL; Receptors, Leukotriene B4; Recombinant Proteins; Spleen

A 35-year-old man from Central America with a history of AIDS and numerous opportunistic infections presented with progressive neutropenia and thrombocytopenia despite having been stable for a period of 6 months. Cessation of antiviral medications did not stop his neutropenia, nor did use of folinic acid, G-CSF, or erythropoietin. The failure of these measures required repeated blood transfusions. Although the physical examination was relatively unremarkable, hematology and blood chemistries indicated that the patient needed urgent hospitalization due to fever and neutropenia. Neutropenia within HIV infection can be confusing, since it may be a result of the infection itself, an adverse effect of drug therapy, or from an opportunistic infection or malignancy. If the cause is not evident, it is wise to seek the etiology first rather than immediately use bone marrow stimulants, such as G-CSF. In this case, an infectious disease specialist made a diagnosis of disseminated histoplasmosis, after which the patient was treated with amphotericin B and released on itraconazole maintenance therapy.

Topics: Acquired Immunodeficiency Syndrome; Adult; Amphotericin B; Antifungal Agents; Erythropoietin; Fever; Granulocyte Colony-Stimulating Factor; Histoplasmosis; Humans; Male; Mucous Membrane; Neutropenia