Release of WBC-derived IL-1 receptor antagonist into supernatants of RBCs: influence of storage time and filtration.

BACKGROUND: Transfusion-associated immunodepression may be related to the transfer of immunoinhibitory cytokines with blood components. STUDY DESIGN AND METHODS: After evidence of increasing concentrations of IL-1 receptor antagonist (IL-1RA) but not of IL-10 was obtained in supernatants of stored RBC units that were WBC-reduced by centrifugation (C-RBCs) in a pilot study, IL-1RA concentrations were determined weekly in supernatants of C-RBCs and in units that underwent prestorage WBC reduction by in-line filtration (F-RBCs) over a 49-day storage. For assessing total IL-1RA content, complete cell lysis by repeated freezing and thawing was done. The results were related to the changes in WBC count during storage. The dependency of IL-1RA content on preparation procedures was assessed. RESULTS: The prestorage IL-1RA concentration in C-RBCs (859 +/- 218 pg/mL) was significantly higher than in F-RBC (75 +/- 13 pg/mL). Whereas no changes were seen in F-RBCs during storage, IL-1RA levels in C-RBC supernatants drastically increased to levels about 50 times those in normal plasma (16,327 +/- 2,686 pg/mL on Day 49). Follow-up analysis revealed stringent correlation between IL-1RA release into supernatants and the current loss of WBCs (r = 0.79, n = 42; p<0.001). The total IL-1RA content did not change during storage and was directly dependent on prestorage WBC count. Preparation procedures altered the IL-1RA content only by WBC reduction. CONCLUSION: The immunosuppressive cytokine IL-1RA is transmitted by RBCs in relation to WBC content and storage time.

A high prevalence of cytomegalovirus antigenaemia in patients with moderate to severe chronic plaque psoriasis: an association with systemic tumour necrosis factor alpha overexpression.

Microbiological aspects are considered to be of pathophysiological importance in psoriasis, but there has so far been no information regarding cytomegalovirus (CMV) infection. This is of interest due to the high prevalence of latent infection in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV. To detect active infection we analysed CMV antigen expression of peripheral blood mononuclear cells (PBMC) from psoriatic patients (n = 30) in comparison with healthy volunteers (n = 65). Using three monoclonal antibodies and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique), we frequently found CMV antigenaemia in psoriasis (43%) compared with healthy laboratory staff (12%, P < 0. 01) and blood donors (6%, P < 0.001). Clearance of CMV antigenaemia was observed with antipsoriatic treatment. CMV antigenaemia was symptomless, and was associated with seropositivity for anti-CMV IgG but not IgM antibodies, indicating subclinical activation of latent infection. Serological investigations in 85 psoriatic patients gave no evidence for a higher prevalence of latent CMV infection. In psoriatic lesions, CMV DNA was only rarely detected by polymerase chain reaction. As it has been shown that tumour necrosis factor (TNF)-alpha can induce CMV reactivation, we determined TNF-alpha plasma concentrations and mRNA expression in PBMC from psoriatic patients. Elevated TNF-alpha levels were found and correlated with the frequency of CMV antigen-expressing PBMC, suggesting a critical role of TNF-alpha in CMV activation. We speculate that active, subclinical CMV infection may be of pathophysiological importance in psoriasis.