a couple of intriguing abstracts re cytokines, including a treatment modality
 

I'm trying to get copies of the articles:

(1) "Successful intravenous regional block with low-dose tumor necrosis factor-alpha antibody infliximab for treatment of complex regional pain syndrome," Bernateck M, Rolke R, Birklein F, Treede RD, Fink M, Karst M Anesth. Analg., 2007 Oct; 105(4):1148-51

Department of Anesthesiology, Pain Clinic, Hannover Medical School, Hannover, Germany. bernateck.michael@mh-hannover.de

Cytokines, particularly tumor necrosis factor-alpha, may play an important role in the mediation of mechanical hyperalgesia and autonomic signs in complex regional pain syndrome 1. We performed an IV regional block with low-dose administration of the tumor necrosis factor-alpha antibody, infliximab, in a patient with typical clinical signs of complex regional pain syndrome 1 (moderate pain, edema, hyperhidrosis, elevated skin temperature compared with the contralateral side). A significant improvement of clinical variables was observed 24 h after infliximab treatment. Almost complete remission was reached within 8 wk, but sensory signs improved only after 6 mo. No adverse events were observed. [Emphasis added.]

(2) "Differential expression patterns of cytokines in complex regional pain syndrome," Uçeyler N, Eberle T, Rolke R, Birklein F, Sommer C., Pain, 2007 Nov; 132(1-2):195-205. Epub 2007 Sep 24.

Department of Neurology, University of Würzburg, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany.

Complex regional pain syndromes (CRPS) are characterized by persistent and severe pain after trauma or surgery. Neuro-immune alterations are assumed to play a pathophysiological role. Here we set out to investigate whether patients with CRPS have altered systemic pro- and anti-inflammatory cytokine profiles compared to controls on mRNA and protein level. We studied blood cytokine mRNA and protein levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF), interleukin-2 (IL-2) and IL-8 and the anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-beta1 (TGFbeta1) in 40 prospectively recruited patients with CRPS I, two patients with CRPS II, and 34 controls. Quantitative real-time PCR and enzyme linked immunosorbent assay were used. Additionally, the patients underwent quantitative sensory testing and were assessed with the McGill pain questionnaire and the Hospital anxiety and depression scale. Patients with CRPS had higher blood TNF and IL-2 mRNA levels (p=0.005; p=0.04) and lower IL-8 mRNA levels (p<0.001) than controls. The mRNA for the anti-inflammatory cytokines IL-4 and IL-10 was reduced in the patient group (p=0.004; p=0.006), whereas TGFbeta1 mRNA levels did not differ between groups. These results were paralleled by serum protein levels, except for TGFbeta1, which was reduced in patients with CRPS, and for IL-8, which gave similar protein values in both groups. Sensory testing showed a predominant loss of small fiber-related modalities in the patient group. The shift towards a pro-inflammatory cytokine profile in patients with CRPS suggests a potential pathogenic role in the generation of pain.

Mike

I have both articles, but each PDF is larger than the maximum size allowed by Neurotalk for uploading in a post. I am happy to email them to people who would like them - please just PM me with your email address.

I think I just may be able to post "Successful intravenous regional block with low-dose tumor necrosis factor-alpha antibody infliximab for treatment of complex regional pain syndrome." Let's find out. (I can also accept requests for a copy of the other article.)

Mike

TY
 

A little hard to follow but sounds good- I just dont know what to do with the info from these articles?

Deb

Dear Deb -

According to Wikipedia, "Infliximab (brand name Remicade) is a drug used to treat autoimmune disorders." See, http://en.wikipedia.org/wiki/Remicade. But there are some potentially significant side effects from the drug, e.g. immune suppression.

I would suggest printing out the articles and discussing the risks and benfits of treatment (which willl vary from person to person) with a rheumatologist of one's choosing.

Mike

Wow..
 

That is so absolutly kool thank you mike for posting this.
hugz,
Sandra

Dear Sandra -

While I appreciate your thanks, in the interest of full disclosure, let me repeat the "Safety" paragraph from the Wkipedia article on Infliximab:

According to the product labeling of Infliximab, Etanercept, and Adalimumab, these drugs are in the class of immunosuppressants. After a number of studies and reports of adverse reactions in patients receiving anti-TNFα therapy (including serious and sometimes fatal blood disorders, infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, rare reports of drug induced lupus and rare reports of demyelinating central nervous system disorders), the FDA issued a warning to doctors appearing in the respective product labeling of these drugs instructing them to screen and monitor potential patients more carefully ([1]). Maintenance therapy with the drug (versus intermittent or sporadic therapy) lessens the likelihood of developing antibodies to infliximab which could reduce the efficacy of the drug. Combination treatment with methotrexate (an anti-folate drug which suppresses the immune system) has been shown to reduce the formation of these antibodies in patients with rheumatoid arthritis [12] and combination therapy with other immunosuppressants has been shown to reduce the liklihood of these antibodies being formed in Crohn's disease. The use of immunosuppressants may not be necessary in all diseases for which infliximab is indicated, and indiscriminant use of these other immunosuppressants carry their own risks. Infliximab was studied in monotherapy (without concommitant immunosuppressants such as methotrexate or azothiaprine) in psoriasis, psoriatic arthritis, and ankylosing spondylitis, and only its use in rheumatoid arthritis requires the concomitant use of methotrexate by FDA product labeling. [Emphasis added.]

1. Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, Scallon B, Moore MA, Vilcek J, Daddona P, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993;30:1443-53. PMID 8232330.

12. ATTRACT RA Trial

Anyone who's interested should also check out the link to the (U.S.) FDA's 45 pages of prescribing drug information, beginning with a great big "black box" warning: http://www.fda.gov/medwatch/safety/2...emicade_PI.pdf

Bottom line, I've known about this stuff for a while now, and have still not taken the plunge. But that doesn't mean I won't. From what I was told by my rheumatologist, a key concern was waiting until the human derived strains were on the market, and I'll confess that it's been a few months since I last checked.

Mike