RESUMO
Objectives: This case-control study investigated the mode of leukocyte function in sickle cell anemia (SCA) to delineate the underlying immunopathology for early diagnosis and mitigate the increased bacterial infection risk in this patient population. Method: In total, 90 participants comprising 24 hemoglobin (Hb)-AA, 22 Hb-AS, 23 steady state Hb-SS and 21 vaso-occlusive crisis state Hb-SS subjects were recruited for this study. The subjects were further divided into the following six groups: Hb-AA and Hb-AS subjects as control groups, Hb-SS subjects at steady state, Hb-SS subjects in a vaso-occlusive crisis state, Hb-SS subjects undergoing medication (Meds), and Hb-SS subjects undergoing medication plus blood transfusion (Meds/BT) group, respectively. Hematological analysis, Hb electrophoresis, leukocyte ratios, and leukocyte functional assays were assessed with standard methods, and interleukin 8 (IL-8) and L-selectin levels were evaluated using enzyme-linked immunosorbent assays. Results: Total leukocyte and monocyte counts were increased in the Hb-SS groups compared to the control groups. However, the Hb-SS groups had lower lymphocyte counts than the other groups (p < 0.005). Leukocyte viability was increased in the SCA groups, while phagocytic activities and oxidative respiratory burst were both reduced in the SCA groups (p < 0.005). Increased IL-8 levels were observed in all SCA groups (p < 0.05), whereas L-selectin levels of the Hb-SS steady and Hb-SS on Meds groups were decreased compared to the other groups (p < 0.05). The neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were higher in the SCA groups than the control groups (p < 0.05). Conclusion: Impaired leukocyte phagocytic and oxidative respiratory burst activities constitute altered leukocyte function in SCA, which can increase their susceptibility to infections and the risk of mortality, especially during the crisis state. Novel therapeutic approaches can be tailored specifically to enhance these leukocyte functions and mitigate the increased infection risk in SCA.
RESUMO
Malaria etiologies with pathophysiological similarities to hypertension currently constitute a major subject of research. The malaria-high blood pressure hypothesis is strongly supported by observations of the increasing incidence of hypertension in malaria-endemic, low- and middle-income countries with poor socioeconomic conditions, particularly in sub-Saharan African countries. Malnutrition and low birth weight with persistent symptomatic malaria presentations in pregnancy correlate strongly with the development of preeclampsia, gestational hypertension and subsequent hypertension in adult life. Evidence suggest that the link between malaria infection and high blood pressure involves interactions between malaria parasites and erythrocytes, the inflammatory process, effects of the infection during pregnancy; effects on renal and vascular functions as well as effects in sickle cell disease. Possible mechanisms which provide justification for the malaria-high blood pressure hypothesis include the following: endothelial dysfunction (reduced nitric oxide (NO) levels), impaired release of local neurotransmitters and cytokines, decrease in vascular smooth muscle cell viability and/or alterations in cellular calcium signaling leading to enhanced vascular reactivity, remodeling, and cardiomyopathies, deranged homeostasis through dehydration, elevated intracellular mediators and proinflammatory cytokine responses, possible genetic regulations, activation of the renin-angiotensin-aldosterone system mechanisms and renal derangements, severe anemia and hemolysis, renal failure, and end organ damage. Two key mediators of the malaria-high blood pressure association are: endothelial dysfunction (reduced NO) and increased angiotensin-converting enzyme activity/angiotensin II levels. Sickle cell disease is associated with protection against malaria infection and reduced blood pressure. In this review, we present the state of knowledge about the malaria-blood pressure hypothesis and suggest insights for future studies.