Th1 and Th2 Cytokine Profiles in Sickle Cell Disease

Abstract

We have investigated the levels of Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines in the plasma and supernatants following peripheral blood mononuclear cell culture and mitogen stimulation in a group of 39 patients with sickle cell disease (SCD) made up of 29 SS, 8 Sβ-thal and 2 Hb SD in steady state. Five SS patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14 were healthy at the time of the study. The plasma levels of IL-2 and IFN-γ were similar in the patients and the controls. However, plasma IL-4 was significantly higher among the steady-state SS patients than in the controls. While there was no significant difference in cytokine levels following mitogen stimulation in the different groups, plasma IL-2 to IL-4 and IFN-γ to IL-4 ratios were significantly lower among the steady-state SS patients, indicating a possible Th2 bias in our sickle cell patients and suggesting a possible mechanism to explain the predisposition of SCD patients to bacterial infections. However, SS patients with good splenic function showed a relative Th1 bias, which may be an additional explanation for the protection against bacterial infections in such patients.

High levels of neopterin and interleukin-3 in sickle cell disease patients

“…In another study elevated levels of IFN-g were observed in steady-state SCD patients compared to normal subjects, but there was no difference between steady-and crisis-state groups (15). In our study patients with SCD presented IFN-g levels similar to those in controls, in agreement with Raghupathy et al (13). The great diversity of IFN-g level determinations in clinical studies is probably due to IFN-g instability and to the technical limitations of plasma detection by current assays.…”

“…Raghupathy et al (13) reported that IFN-g plasma levels are similar in SS patients and controls, and Taylor et al (14) observed lower IFN-g levels in steady-and crisis-state SCD patients. In another study elevated levels of IFN-g were observed in steady-state SCD patients compared to normal subjects, but there was no difference between steady-and crisis-state groups (15).…”

Asthma in children with sickle cell disease and its association with acute chest syndrome

“…It is therefore tempting to speculate that SCD children with atopic asthma may be predisposed to recurrent ACS; this may be due to an underlying Th2 profile as increased plasma levels of interleukin 4 are more common in patients with SCD than controls. 31 There are, however, no data regarding Th2 status and ACS episodes; this merits investigation.…”

Dysregulated Arginine Metabolism, Hemolysis-Associated Pulmonary Hypertension, and Mortality in Sickle Cell Disease

“…5 Association of arginase activity with common markers of inflammation such as white blood cell count and myeloperoxidase is not unexpected because arginase is induced in monocytes in response to helper T-cell type 2 cytokines, 24 inflammatory mediators that are elevated in SCD. 55 Elevated arginase activity has also recently been discovered in asthma, [56][57][58][59] another T-cell type 2 cytokine-related disorder 60,61 that may be relevant to the pathophysiology of SCD since 30% to 70% of pediatric patients with SCD have reactive airways. 62,63 An association of arginase activity with plasma soluble adhesion molecules is a novel observation, although also not unexpected since endothelial cells assume an inflammatory phenotype in SCD.…”