Modulation of cytokine profiles by malaria pigment – hemozoin: role of IL-10 in suppression of proliferative responses of mitogen stimulated human PBMC

Suppression of Prostaglandin E2by Malaria Parasite Products and Antipyretics Promotes Overproduction of Tumor Necrosis Factor–α: Association with the Pathogenesis of Childhood Malarial Anemia

“…Consistent with previous reports [26][27][28][29][30], the present study shows that ingestion of pfHz and sHz by human blood mononuclear cells increases TNF-a production. The results presented here demonstrating that exogenous PGE 2 dose-dependently decreases TNF-a production in sHz-treated PBMCs provide direct evidence that suppression of PGE 2 allows overproduction of TNF-a.…”

“…Because previous studies indicate that pfHz and sHz increase TNF-a production in cultured human mononuclear cells [26][27][28][29][30], and that PGE 2 inhibits TNF-a transcription [16,17], we determined whether TNF-a levels would be elevated under identical experimental conditions that suppressed PGE 2 formation. Addition of pfHz and sHz to PBMCs dose-dependently increased baseline TNF-a production ( and , re-P !…”

Increased circulating interleukin (IL)-23 in children with malarial anemia: In vivo and in vitro relationship with co-regulatory cytokines IL-12 and IL-10

“…A number of studies from our laboratory [27][28][29]38], as well as others [49][50][51], have shown that Hz is an important parasitic product that causes dysregulation of de novo cytokine production in human PBMC. As such, Hz was examined as a potential parasitic product that could alter the transcriptional expression of IL-23, IL-12, and IL-10.…”

Acquisition of Hemozoin by Monocytes Down-Regulates Interleukin-12 p40 (IL-12p40) Transcripts and Circulating IL-12p70 through an IL-10-Dependent Mechanism: In Vivo and In Vitro Findings in Severe Malarial Anemia

“…Previous studies with cultured PBMC demonstrated that phagocytosis of Hz causes dysregulation in IL-12, IL-10, and TNF-␣ production (3,11,15,16,26,35,40), suggesting that the acquisition of Hz by blood mononuclear cells may be responsible for the altered levels of cytokine production observed in children with natural infections. To extend these findings and to determine the importance of cellular interactions between monocytes and lymphocytes, in vitro experiments were performed with cultured PBMC and CD14 ϩ and CD14 Ϫ cells from malaria-naïve donors.…”

“…Phagocytosis of parasitic products, such as P. falciparumderived malarial pigment (hemozoin [PfHz]), alters IL-12, IL-10, and TNF-␣ production in cultured human peripheral blood mononuclear cells (PBMC) (3,11,15,16,26,35,40), suggesting that acquisition of PfHz by monocytes/macrophages may be an important source of cytokine dysregulation during malaria. Hz is an insoluble coordination polymer of heme subunits formed during hemoglobin (Hb) catabolism by Plasmodium to avoid the toxic effects of heme (41).…”