For those of us with viral involvement (as defined by all herpes viruses, HHV6, CMV, etc and enteroviruses EV71, Coxsackie B3, etc.), it is my belief that part of what might help us lies in understanding COX-2. I dropped my enormously elevated HHV6 titer by 2/3 and CMV Igg and Igm to negative. I accomplished this, in part, through the use of a COX-2 inhibitor and and ARB. I think the confusion in the literature about the role of COX2 in immunity is because it differentially affects different wings of the immune system. COX2 is an activator of TH2 immunity, its actually required for generation of antibodies through endosomal TLR9. On the other hand, it cripples TH1 immunity through the immunosuppressive prostanoid PGE2 (endoperoxidase, ie COX, catalyzes the conversion of arachidonic acid to PGE2) which, interestingly, is the prostanoid that biases the NK cells (and other effector cells) from an aggressive to tolerant phenotype in mammalian pregnancy (sound familiar?). It is secretory and signals in a paracrine manner.Tumors secrete massive amounts of PGE2 which is one of the ways that cancers lead to systemic immune suppression via COX2/PGE2/PKA, etc. ultimately leading to expression of indoleamine 2,3 dioxygenase (IDO), tryptophan catabolism into kynurenine, which was just discovered to be the endogenous ligand for the aryl hydrocarbon receptor, the activation of which results in the robust generation of Regulatory T cells (again, sound familiar?) which leads to a self sustaining loop of immune tolerance (suppression). I can tie most of the other white cell subsets into this loop, but basically, the alternatively activated phagocytes and Tregs can influence most effector subsets. They are good in tissue healing, graft acceptance and pregnancy but bad in cancer, etc.Diseases where this robust increase in Tregs and general immune suppression becomes highly problematic include cancer, HIV and CFS, all of which have massive increases in Treg suppressiveness and numbers and significantly inhibited NK cell cytotoxicity (not dissimilar to pregnancy). In these conditions, I believe this tolerance must be broken. Celebrex, for example, is impressive in several types of cancer, but its early days. You can see how infected phagocytes can cripple other aspects of the immune system in a paracrine manner. Its interesting to note that less than 1 in 100,000 white cells are actually infected in AIDs patients, but they have huge amounts of circulating PGE2 and IDO.Also of note, PGE2 is involved in pain nociception. Minocycline is a PGE synthase inhibitor, which is why I suspect it reduces symptoms for some people. On the other hand, because it is a PGE synthase inhibitor, there could be some restoration of effector function, which may lead to an increase in symptoms. Interestingly, both minocycline and celebrex improve DHT reactions in AIDs patients.The literature indicates the following data in humans: COX-2 is hyper activated in white cells of CFS patients. Circulating TRegs are increased. Natural killer cell numbers and cytotoxicity are reduced. Anti-body production is amplified. All can be reduced by inhibition of COX-2, but most of the tools used for this purpose are blunt and have side effects.Virtually all herpes viruses induce COX-2 (as does HIV) generating PGE2. PGE2 signals in an endocrine/paracrine manner and has broad based blunting effects on innate immunity through binding of the EP2 and EP4 receptors, activation of adenlyl cyclase and increases in cyclic AMP through PKA. Interestingly, catecholamines do the same thing through the beta adrenergic receptors. Interesting that stress increases herpes breakouts. PGE2 is actually being used in allogenic stem cell transplants to block the immune response (primarily NK cells) to donor cells.In the lab, CMV replication can be reduced by 100 fold with selective COX-2 inhibitors. Addition of PGE2 to HHV6 cell culture dramatically increases its replication in a cAMP dependent manner. COX-2 inhibitors also inhibit the expansion of EBV positive and KSHV infected lymphoblastoid cells and regress CMV positive tumors in mice. EV71 is also dependent upon COX-2 activity to replicate, etc.There was a recent patent which indicated that vioxx and other COX-2 inhibitors may have caused a reactivation or immune response to latent herpes (CMV) infection in the vasculature, namely the heart. There are also papers which mention targeting this enzyme in lieu of typical anti-viral meds.I used a pulsed approach of celebrex (alternate days) along with and angiotensin receptor blocker to dampen excessive inflammation. I believe that breaking immune tolerance to pathogens should be done gradually. Initially, I felt feverish, achy, super tired, etc. Eventually, I felt stronger and my blood work showed improvement after showing no improvement for years.Tissue damage increases COX-2 which increases the replication of many viruses, which increases tissue damage, etc. etc. I suspect this is what happens in chronic enterovirus infections in the gut.Of course, we all know that there can be bad side effects to inhibiting this pathway. Just sharing my intro thoughts.More later. Thanks for this great forum, btw.NOTE: I am not a professional nor am I providing any type of medical advice nor advocating the use of any kind of drug. Just sharing my thought on research and personal experiences.