TY  - JOUR
AU  - Netea, M.G.
AU  - Brouwer, A.E.
AU  - Hoogendoorn, L.
AU  - Meer, J.W.M. van der
AU  - Koolen, M.
AU  - Verweij, P.E.
AU  - Kullberg, B.J.
PY  - 2004
UR  - https://hdl.handle.net/2066/59191
AB  - BACKGROUND: Although Cryptococcus neoformans is a fungal pathogen that causes human disease predominantly in the immunocompromised host, severe cryptococcal infections are occasionally encountered in apparently immunocompetent individuals. Activation of cellular immunity by proinflammatory cytokines plays a central role in anticryptococcal defense. METHODS: We describe 2 patients with severe cryptococcal meningitis who appeared to have idiopathic CD4 lymphopenia. For these patients and for 4 healthy volunteers, ex vivo stimulation of whole blood with microbial stimuli was used to investigate putative defects in cytokine production capacity. RESULTS: Assessment of the cytokine released from the 2 patients with CD4 lymphopenia revealed a defective production of the proinflammatory cytokines interferon (IFN)- gamma and tumor necrosis factor (TNF) but not of the anti-inflammatory cytokine interleukin-10 (IL-10). One patient with disease progression despite receipt of antifungal treatment was administered immunotherapy with recombinant IFN- gamma . Administration of recombinant IFN- gamma resulted in both restoration of immunological parameters and a sustained clinical recovery. CONCLUSIONS: Refractory meningitis may be due to defective TNF and IFN- gamma production, and IFN- gamma treatment may be useful in patients with an impaired cellular immune response and refractory cryptococcal meningitis.
TI  - Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia: defective cytokine production and reversal by recombinant interferon- gamma therapy.
EP  - 7
SN  - 1058-4838
IS  - iss. 9
SP  - e83
JF  - Clinical Infectious Diseases
VL  - vol. 39
DO  - https://doi.org/10.1086/425121
ER  - 
TY  - JOUR
AU  - Kullberg, B.J.
AU  - Oude Lashof, A.M.L.
AU  - Netea, M.G.
PY  - 2004
UR  - https://hdl.handle.net/2066/58102
AB  - Resolution of invasive fungal infections is often dependent on recovery from an immunocompromised state, which indicates that host defense mechanisms are extremely important in the clearance of fungal pathogens. Immunotherapy aimed at enhancement of host defense mechanisms may improve clinical outcome of invasive mycoses. The design of trials of immunotherapy against fungal pathogens requires profound knowledge of the host defense mechanisms that are involved in invasive fungal infections. Prospective phase II studies with recombinant granulocyte colony-stimulating factor and interferon-gamma have been done. Recombinant interferon-gamma is a candidate for phase III trials of adjunctive immunotherapy for cryptococcal meningitis, invasive aspergillosis, and candidemia, but the proper design of future trials will be crucial to establish whether immunotherapy is of clinical value in the treatment of invasive fungal infections.
TI  - Design of efficacy trials of cytokines in combination with antifungal drugs.
EP  - 23
SN  - 1058-4838
IS  - iss. suppl. 4
SP  - S218
JF  - Clinical Infectious Diseases
VL  - vol. 39 Suppl 4
DO  - https://doi.org/10.1086/421960
ER  -