Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis. An update and proposals for guidelines.

The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is well documented. Efficacy and adverse effects are both dose dependent. and adverse effects rather than lack of efficacy are the main reason for discontinuing therapy. Several adverse effects are related to folate deficiencies, largely due to the antifolate properties of methotrexate. In order to reduce adverse effects without compromising drug efficacy, numerous clinical investigations have been performed using supplementation with folic or folinic acid during methotrexate therapy of patients with rheumatoid arthritis, addressing both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Based on these studies, an individually adjusted supply of folic acid rather than folinic acid is proposed. For many patients, however, a properly balanced diet is sufficient to avoid folate deficiency.

[Methotrexate and folates in rheumatoid arthritis]. / Metotreksat og folater ved reumatoid artritt.

The efficacy of weekly low-dose methotrexate treatment of rheumatoid arthritis is well documented. Efficacy and adverse events are both dose dependent, and side effects rather than lack of response are the main reason for discontinuing therapy. Several adverse effects appear to be related to folate deficiencies, and are largely due to the antifolate properties of methotrexate. In order to diminish side effects without compromising drug efficacy, clinical trials have been performed using folic acid or folinic acid concomitantly with methotrexate. Important to this achievement are both the timing of folate supplementation and the weekly folate-to-methotrexate ratio. Considering these and other factors, an individually adjusted supply of folic acid is proposed. For several patients a properly balanced diet is sufficient; they do not need additional folate supplements when using methotrexate.

Interleukin-6 in synovial fluid from patients with arthritis.

Synovial fluid and serum from patients with rheumatoid arthritis, other inflammatory arthritides, and traumatic arthritis were assayed for the presence of interleukin-6 (IL-6) by means of an IL-6-dependent mouse hybridoma cell line. The cytokine was detected in all the samples of synovial fluid (range 50-22000 U/ml). IL-6 in synovial fluid was positively correlated (r = 0.58, P = 0.03) with the erythrocyte sedimentation rate in patients with inflammatory arthritis. In serum, the concentration of IL-6 was slightly elevated in some patients with rheumatoid arthritis. The results demonstrate that IL-6 is released into synovial fluid in joints affected by arthritis, and there appears to be an association between the levels of IL-6 and disease activity.

Gastrointestinal peptides in serum and synovial fluid from patients with inflammatory joint disease.

The concentrations of immunoreactive vasoactive intestinal polypeptide (ir-VIP), immunoreactive pancreatic polypeptide (ir-PP), ir-somatostatin, and ir-secretin were measured in serum and synovial fluid from patients suffering from various inflammatory joint diseases. One group of patients were not taking any medication, while another group received anti-inflammatory treatment at the time of sampling. High levels of ir-VIP in the synovial fluid were observed in the untreated group of patients, and the concentration of ir-VIP in the synovial fluid was significantly higher than in parallel serum samples. On the other hand, no significant differences in the concentrations of the other peptides were observed either between serum and synovial fluid or between the two groups of patients. It is suggested that VIP is released locally at the inflammatory site and that VIP may be of significance in inflammatory disorders.

The complete amino acid sequence of a prototype immunoglobulin-lambda light-chain-type amyloid-fibril protein AR.

The amino acid sequence of an amyloid-fibril protein of immunoglobulin light-chain type (AL) was elucidated. The sequence determination involved digesting the protein with trypsin, thermolysin and pepsin. The protein was found to consist of 154 amino acid residues and is thus missing about half of the constant region of a light chain. A certain heterogeneity in the length of the polypeptide was observed in the C-terminal region. The amino acid sequence from CDR (complementary-determining region) 1 and FR (framework region) 3 indicated an oligoclonal origin of the protein. By comparing the primary structure of protein AR with other lambda- and even kappa-chains, it was revealed that protein AR had an insertion of two residues of aspartic acid, namely residues 68 and 69, which has not been reported previously in light chains. The overall sequence homology in the variable region showed that protein AR is more similar to V lambda V than to the other subgroups [Kabat, Wu & Bilofsky (1979) Variable regions of Immunoglobulin Chains, Medical Computer Systems, Bolt, Beranek and Newman, Cambridge, MA].