Pathophysiology of visceral leishmaniasis - some recent concepts.
Visceral leishmaniasis is characterized by diversity and complexity of clinical manifestations ranging from asymptomatic infection to life threatening illness. Experimental evidence and clinical studies indicate multifaceted role of various factors leading to parasite survival and multiplication. In early stage of infection, generation of reactive oxygen and nitrogen intermediates play significant role in curtailing the parasite multiplication while in later phase on one hand, hepatic resistance is expressed by the dominant role played by nitric oxide synthase (NOS)-2 gene regulation and on the other hand, production of inhibitors of NOS-2 gene expression, interleukin 10 (IL-10) and transforming growth factor beta (TGFbeta) correlate well with reduced parasite killing. The hepatic infection is usually self-limiting due to production of multiple cytokine responses including moderate level of tumour necrosis factor (TNF) while in spleen excess TNF mediates destructive pathology. CD8+ T cells appear to play multiple roles comprising both cytotoxic activity and secretion of cytokines and chemokines. Capacity to produce ThI cytokines is associated with asymptomatic or subclinical self-healing infection. However, in symptomatic patients, Th I cytokine production is not depressed but there appears to be unresponsiveness to the stimuli of these cytokines. Experimental evidences indicate genetic basis for such a phenomenon.
Malla
Nancy
N
Department of Parasitology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
Mahajan
R C
RC
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007107:Immune System; D007891:Leishmania; D007898:Leishmaniasis, Visceral / Q000175:diagnosis / Q000469:parasitology / Q000503:physiopathology*; D008214:Lymphocytes / Q000276:immunology / Q000469:parasitology; D013154:Spleen / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines