Profiles of Cytokines (TNFα and IL-6) and Acute Phase Proteins (CRP and α1AG) related to the Disease Course in Patients with Systemic Lupus Erythematosus

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Abstract
Tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNFα and IL-6 in relation to serum levels of C-reactive protein (CRP) and α1-acid glycoprotein (α1AG) in three systemic lupus erythematosus (SLE) patients. Disease courses of these patients were divided in a total of 19 clinical periods, according to the clinical symptoms and interleukine profiles. Significantly elevated TNFα levels were found in all but three of the defined periods, without being associated with disease activity. In only four of the defined periods elevated TNFα were observed combined with elevated IL-6 and CRP levels. Two of these periods coincided with minor symptoms of SLE, one with an exacerbation and the other one with a systemic infection while SLE activity was low. All other periods showed varying combinations of elevated TNFα and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised α1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNFα and IL-6 and also between the different cytokine (TNFα and IL-6) levels and acute phase protein (CRP and α1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNFα and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE. These data are also highly suggestive of an imbalance between TNF, IL-6 and the acute phase reaction.