#tnf-a

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Potential Adverse Drug Reactions: TNF-a inhibitors -TNF-a inhibitors are used to treat some inflammatory conditions, but are contraindicated in SLE (lupus). -TNF-a inhibitors may result in anti-TNF-a-induced lupus. -Before anti- TNF therapy, baseline ANA, etc. should be done to make sure patients do not have lupus, and follow up should watch for the possible development of lupus. -"Most cases of ATIL are caused by infliximab, followed by etanercept and adalimumab." (Almoallim et al.)

Potential ADR: TNF Antagonist Drugs "TNF antagonists have had dramatic effects on the suppression of rheumatoid arthritis and other rheumatic inflammatory diseases. However, TNF inhibition of RA has led to an increased incidence of drug induced anti-dsDNA production, with cases of systemic lupus erythematosus as well as exacerbations ofmultiple sclerosis. While etanercept does not generally alter the course of Crohn's disease we describe a rare instance where this agent may have contributed to the development of clinically significant inflammatory bowel disease." (Oh et al.)

Headache Types & Inflammation: "New daily persistent heqdache (NDPH) is considered one of the most treatment resistant of all headache syndromes. . . As a certain percentage of NDPH patients have their headaches start after an infection, the possibility of a persistent state of systemic or CNS inflammation comes into question." "TNF alpha is a proinflammatory cytokine involved in brain immune and inflammatory activities, as well as in pain initiation. . . An elevation of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role for TNF alpha in the pathogenesis of this condition. Surprisingly, all chronic migraine (CM) and post-traumatic headache (PT) patients tested had elevated CSF TNF alpha levels. . . . All of these syndromes may be manifestations of CNS inflammation." "As most of the positive-tested patients showed minimal to no improvement during aggressive inpatient treatment, persistent elevation of CSF TNF alpha levels may be one of the causes of treatment refractory CDH." (Rozen & Swidan) (They may need to try different classes of medicines than those they may normally use to try to treat headache.)

IVIG is used to treat some immune deficiencies, like CVID, and is being tried in some autoimmune and inflammatory disorders including in some fibromyalgia patients. The ways it may benefit some patients are not fully understood, and these reports on the effect on inflammation are contradictory. IVIG has an antiinflammatory action in CVID patients. . . "The cytokine level in the supernatants of peripheral blood mononuclear cells (PBMC) after ex vivo LPS stimulation demonstrated the >2-fold decrease in TNF production 4h after IVIG." It was decreased in 4/7 patients. "In vitro exposure of the healthy individuals' monocytes to the IVIG preparation resulted in reduced TNF production. . . . " (Siedlar et al.) vs IVIG does NOT have an antiinflammatory action in CVID . . . "This increase in TNF-alpha and IL-2, combined with unchanged IFN-gamma expression, is evidence against the putative 'anti-inflammatory' role of IVIG, and may explain the failure of resolution of granulomata in CVID patients treated with IVIG alone." (Sewelll et al.) (They found lower vs higher TNF-a after IVIG. TNF-a levels are important because it can influence immunoglobulin levels and play a role in some inflammatory conditions.) Links to studies: "Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients" -Clin Immunol 2011 http://www.ncbi.nlm.nih.gov/pubmed/21300572 vs "In vivo modulation of cytokine synthesis by intravenous immunoglobulin" -Clin Exp Immunol 1999 http://www.ncbi.nlm.nih.gov/pubmed/10361243

Painful Periods: & "Excessive Inflammatory Response" Upregulation of genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) play a role in menstrual pain. (Ma et al.) (Cytokines are inflammatory immune cells that also play a role in some diseases.)

Mast Cells & Mast Cell Inhibitors: Quercetin (Que), " . . . is a promising candidate as an effective mast cell inhibitor for allergic and inflammatory diseases . . . " "Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF." This study compares cromoglycate (cromolyn), a medicine known as a mast cell "stabilizer", verses quercetin, a flavonoid, and,"flavonoids are potent anti-oxidant and anti-inflammatory compounds with mast cell inhibitory actions." Quercetin (Que) and cromolyn inhibited histamine, leukotrienes and PGD(2) release from mast cells. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release . . . Moreover, Que reduces IL-6 release . . ." In two trials, "Que significantly decreased contact dermatitis and photosensitivity, skin conditions that do not respond to conventional treatment." (Weng et al.) (Anecdotally, a number of FM patients i have spoken to have food allergies. IgE produced in allergies can stimulate mast cells. In addition, some FM patients have been found to have increased mast cells in their skin and increased inflammatory immune cells.)