The Interferon Compartment of the Immune Response in Human Malaria: II. Presence of Serum-Interferon Gamma Following the Acute Attack

Abstract

The present study concerns the monitoring of serum-interferon (serum-IFN) levels among 189 patients followed after and sometimes during an acute episode of malaria due mainly to Plasmodium falciparum (P. falciparum). Of these patients, 110 known to have no other parasitic or infectious disease were followed in France; 79 were from Thailand, among which 25 cases of neuromalaria were diagnosed. In a first four-month survey conducted in France, among 100 patients seen after the acute attack, serum-IFN-gamma was characterized among 87% cases for which at least two sera were controlled, whereas in a healthy population no serum-IFN was present. When efforts were concentrated on screening ten cases during the first 48 h of the febrile attack, serum-IFN-alpha was mainly characterized, whereas serum-IFN-gamma was present only once. Elevated leukocyte 2',5' oligoadenylate synthetase levels were found among several IFN-alpha positive patients of this study group. A peculiarity pertaining to the patients from Thailand was that one-third (25 cases) were cerebral malaria cases. Among these, 15 were followed under hospitalization during the first 96 h. In this study group, the onset of circulating immune interferon was found to be preceded or accompanied by that of IFN-alpha. Thus, if serum-IFN-gamma is largely characterized among malaria patients followed after the acute attack, it is possible that the onset of circulating immune interferon is generally preceded by that of IFN-alpha.

Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge.

“…Most investigators have found no correlation of serum IFN-'y levels with parasite density, disease severity, or the occurrence of cerebral involvement in patients with malaria (21,24,(34)(35)(36). In the present study, IFN-y levels had normalized in the parasitemic volunteers before parasite density could increase or serious complications could develop, and a triggering role for IFN-y in severe malaria could conceivably be missed in clinical studies due to its transient and early nature.…”

“…Ethical considerations dictated prompt treatment of the parasitemic volunteers early in their illness. The studies reported here therefore differ from those done previously in field settings in which cytokirie levels were evaluated in patients primarily after they had become ill ( 14,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

“…To explore the role of cytokines in the presumed immunopathology of human malaria, investigators have studied serum cytokine levels in a variety of clinical settings in patients with malaria ( 14,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36). These studies have been of necessity primarily cross-sectional, done after the onset of symptoms and the initial stages of clinical illness.…”

Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor.

“…Our present observations indicate that the contribution of T cells consists at least in part in producing IFN-'y. Production of IFN-y, which is related to T-cell activation, has been described during murine malaria infection, and elevated levels of IFN-y have been reported in the serum of patients with malaria (13,14). It is evident from in vitro and in vivo studies that both IFN-y and TNF can participate in the killing of malaria parasites inside erythrocytes (15).…”

Expression Microarray Analysis Implicates Apoptosis and Interferon-Responsive Mechanisms in Susceptibility to Experimental Cerebral Malaria

“…65 Genetic association studies have linked IFN-␣ receptor polymorphisms with protection from CM in an African population. 66 In addition, IFN-␣ levels have been detected in PbA 67 and P. falciparum infections, 68 with lower levels of IFN-␣ observed in cases of severe malaria. 41 Little is known about the relationship between type I interferon responses and malarial disease, but type I interferon responses may play a beneficial role for the host in malaria.…”