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Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma
A E Brown1, H K Webster, P Teja-Isavadharm
1Department of Immunology and Biochemistry, U.S. Army Medical Component Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
Abstract:
Macrophage activation during acute falciparum malaria in 71 Thai adults was investigated by measuring urinary neopterin and serum interferon-gamma (IFN-gamma). Neopterin, a product of IFN-gamma-activated macrophages, was elevated in 94% of patients upon admission (day 0, prior to treatment) and in all at some time during the period of study. Neopterin levels tended to rise further (days 1-5) before falling back towards the normal range as patients recovered following effective chemotherapy (days 6-8). IFN-gamma was measured in 32 patients and found to be directly related to neopterin concentration. Both neopterin and IFN-gamma values were highest in patients experiencing a first malaria infection. Among those with histories of prior malaria, neopterin and IFN-gamma levels were inversely related to the number of previous infections. Morbidity, as assessed by degree and duration of fever, was directly related to neopterin concentration. This longitudinal study quantitatively describes the extent and duration of macrophage activation in falciparum malaria. The data also suggest that with repeated malaria infection and antigen exposure, there is a progressive decrease or possibly suppression of the T cell-macrophage interaction mediated by IFN-gamma.
Insights
Acute falciparum malaria activates macrophages, indicated by elevated neopterin and interferon-gamma (IFN-gamma). Levels were highest in first-time infections and decreased with repeated exposure, suggesting suppressed immune responses.
Area of Science:
- Immunology
- Infectious Diseases
- Tropical Medicine
Background:
- Macrophage activation is a key immune response in malaria.
- Interferon-gamma (IFN-gamma) is a critical cytokine involved in macrophage activation.
- Urinary neopterin serves as a biomarker for IFN-gamma-driven macrophage activation.
Purpose of the Study:
- To investigate macrophage activation in acute falciparum malaria.
- To correlate neopterin and IFN-gamma levels with disease severity and infection history.
- To understand the impact of repeated malaria infections on immune responses.
Main Methods:
- Longitudinal study of 71 Thai adults with acute falciparum malaria.
- Measurement of urinary neopterin levels.
- Measurement of serum interferon-gamma (IFN-gamma) in a subset of patients.
Main Results:
- Elevated neopterin detected in 94% of patients at admission, and all during the study.
- Neopterin and IFN-gamma levels correlated directly with each other and were highest in patients with their first malaria infection.
- Higher neopterin levels correlated with increased fever severity and duration.
- Prior malaria infections were associated with lower neopterin and IFN-gamma levels.
Conclusions:
- Macrophage activation is a significant feature of acute falciparum malaria.
- Immune responses, particularly IFN-gamma mediated T cell-macrophage interaction, may be suppressed with repeated malaria infections.
- Neopterin and IFN-gamma levels can serve as quantitative markers for assessing immune activation and its modulation in malaria.