Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia: defective cytokine production and reversal by recombinant interferon- gamma therapy.
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.
Netea
Mihai G
MG
Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen University Center for Infectious Diseases, Nijmegen, The Netherlands.
Brouwer
Annemarie E
AE
Hoogendoorn
Elizabeth H
EH
Van der Meer
Jos W M
JW
Koolen
Marianne
M
Verweij
Paul E
PE
Kullberg
Bart Jan
BJ
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D011994:Recombinant Proteins; D018344:T-Lymphocytopenia, Idiopathic CD4-Positive / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; D011994:Recombinant Proteins; D007371:Interferon-gamma