Tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) play a main role in inducing acute phase protein production by hepatocytes. This study describes the serum levels of TNF alpha and IL-6 in relation to serum levels of C-reactive protein (CRP) and alpha 1-acid glycoprotein (alpha 1AG) 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 interleukin profiles. Significantly elevated TNF alpha 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 TNF alpha 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 TNF alpha and/or IL-6 levels being followed or not by elevated CRP levels. Significantly raised alpha 1AG levels were measured in all clinical periods. In most of the observed periods a dissociation was found between TNF alpha and IL-6 and also between the different cytokine (TNF alpha and IL-6) levels and acute phase protein (CRP and alpha 1AG) levels. These data could not be explained by differences in disease course or influences of medication. We conclude that more factors other than TNF alpha and IL-6 must play a role in the regulatory pathway of the acute phase response in SLE.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal fatty acid binding protein (I-FABP) indicates barrier integrity. Aims: determine if I-FABP is elevated in active Crohn's disease (CD) and if I-FABP parallels anti-TNFα antibody (infliximab) induced lowering of TNFα and Harvey-Bradshaw Index (HBI) as potential indicator of mucosal healing. I-FABP distribution along human gut was determined. Serum from 10 CD patients collected during first three consecutive infliximab treatments with matched pretreatment and follow-up samples one week after each treatment and corresponding HBI data were analyzed. I-FABP reference interval was established from 31 healthy subjects with normal gut permeability. I-FABP and TNFα were measured by ELISA; CRP was measured by nephelometry. Healthy tissue was used for I-FABP immunohistochemistry. Pretreatment CD patient TNFα was 1.6-fold higher than in-house reference interval, while I-FABP was 2.5-fold higher, which lowered at follow-ups. Combining all 30 infusion/follow-up pairs also revealed changes in I-FABP. HBI followed this pattern; CRP declined gradually. I-FABP was expressed in epithelium of stomach, jejunum, ileum, and colon, with the highest expression in jejunum and ileum. I-FABP is elevated in active CD with a magnitude comparable to TNFα. Parallel infliximab effects on TNFα, HBI, and I-FABP were found. I-FABP may be useful as an intestine selective prognostic marker in CD.

In vitro models have shown that interleukin-6 (IL-6) is the main dominator of the stimulation of the full spectrum of acute phase proteins. This study describes IL-6 levels in relation to levels of acute phase proteins in 15 systemic lupus erythematosus (SLE) patients, with special attention given to those patients with increased serum levels of IL-6. Three episodes with elevated levels of IL-6 were observed in a period shortly after a flare-up of SLE, in three of the 15 patients. In one of these three patients a clear increase in the C-reactive protein (CRP) level, preceded by an IL-6 increase, was observed. In the other two patients, CRP levels remained unchanged. It is speculated that, next to IL-6, another signal is operative or needed for the start of an acute phase reaction. However, influences of the disease itself or of the administered therapy cannot be excluded as the cause of the described discrepancy between IL-6 and acute phase protein profiles in these two SLE patients.