Transient immunosuppression

Involution of thymus and suppression of cellular and humoral activity and transient immunosuppressive effects within 2 days of injection with responses returning to normal within a few days... 

Smidi TA, White BD, Gardner JM, Kaleko M, McClelland A (1996c) Transient immunosuppression permits successful reped-dve intravenous admiriistradori of an adenovirus vector. Gene Ther 3 496-502. 

Halbert CL, StandaertTA, Wilson CB, Miller AD. SuccessMreadmiiiistrationofadeno-associated vims vectors to the mouse lung requires transient immunosuppression during the initial exposure. J Virol 1998 72 9795 9805. 

Immune response Cell-mediated response Humoral response HD Ad vectors, PEGylation Transient immunosuppression with CTLA4, CD40 ligand seroswitching stealth Ad vectors (PEGylation) IL-12 and lEN... 

Kaplan JM, Smith AE. Transient immunosuppression with deo spergualin improves longevity of transgeire expression and abihty to readminister adeno viral vector to the mouse lung. Hum Gene Ther 1997 8 1095-1104. 

The islet cells transplanted into humans are obtained from pancreatic tissue of deceased human donors (Figure 8.9). Implantation of these cells in recipients displaying a competent immune system would, at best, be of transient therapeutic benefit. The ensuing immune response would quickly destroy the foreign cells. Studies conducted thus far in humans have utilized diabetic patients who have received kidney transplants, as these are already subject to immunosuppressive therapy. However, a major stumbling block to the widespread adoption of this therapeutic approach is, predictably, the requirement to induce concurrent immune suppression. 

Pimecrolimus (SDZ ASM 981, Elidel) is another recently approved macrolide immunosuppressant that acts by inhibiting calcineurin and blocking the release of proinflammatory cytokines from T lymphocytes. The parent compound, ascomycin, was originally isolated from Streptomyces hygroscopicus var ascomyceticus. Like tacrolimus, pimecrolimus is approved for the topical treatment of moderate to severe atopic dermatitis that is refractory to other therapies. Transient local irritation is a common side effect. 

One case of Staphylococcus aureus meningitis, a rare complication of epidural analgesia, has been published. The same patient developed a cauda equina syndrome of uncertain etiology, although neural ischemia as a result of meningitis secondary to immunosuppression was possible (SEDA-21,420 456). A unique case of transient profound paralysis after epidural glucocorticoid injection (acute paraplegia) has now been reported (SEDA-22, 451 457). Diplopia associated with the peridural or intrathecal infiltration of prednisolone have not been previously reported (SEDA-22, 451 458). 

In children one advantage of tacrohmus is that it can reduce the dose of glucocorticoids required for immunosuppression. This in turn improves growth. When in one center the immunosuppression protocol was changed to tacrolimus plus mycophenolate mofetU and prednisone, two patients developed transient encephalopathy associated with tacrolimus (35). In both cases, the encephalopathy was managed by treating the associated hypertension and fluid overload tacrolimus was not withdrawn. 

Signal transduction by IL-10 is stfll unknown but likely to involve the JAK family of kinases. The signal transduction cascades initiated by IL-10 ligation to its cognate receptor seem to rapidly and transiently stimulate phosphatidylinos-itol 3-kinase activity associated with the p85 subunit of the enzyme. IL-10 also activates p70 S6 kinase that is inhibited by the immunosuppressive drug rapamycin. ... 

The immunosuppressant cyctosporin A, which downregulates activated microglia94 and protects against neuronal and muscarinic receptor losses in the gerbil hippocampus after transient global ischaemia.115... 

Ogawa, N., Tanaka, K., and Kondo, V., The preventative effect of cyclosporin A, an immunosuppressant, on the late onset reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischaemia, Neurosci. Lett., 152, 173, 1993. 

The most common patient complaints with topical tacrolimus therapy are transient itching and burning at the site of application. Although no data support the practice, many clinicians recommend pretreatment with topical corticosteroids to prevent or reduce tacrolimus-induced burning and erythema. Systemic adverse effects of tacrolimus, while well documented with oral therapy, have not been observed in patients using the topical ointment for AD. Patients who receive long-term systemic immunosuppressants are prone to devel-... 

Muraille E, De Smedt T, Andris F, Pajak B, Armant M, Urbain J, Moser M, Leo O Staphylococcal enterotoxin B induces an early and transient state of immunosuppression characterized by V beta-unrestricted T cell unresponsiveness and defective antigen-presenting cell functions. J Immunol 1997 158 2638-2647. 

Interestingly, the pro-apoptotic effects of Bad are blocked by the immunosuppressants cyclosporin (CsA) and FK506. In a model of transient ischemia/reperfusion following middle cerebral artery occlusion, both compounds reduced cerebral infarct volume to 30% of control (49). Blockade of calcineurin-mediated dephosphorylation of Bad is a potential mechanism for this effect. Thus phosphorylated, Bad remains sequestered in the cytoplasm and is unable to bind to Bcl-2 (or Bcl-XL), thereby allowing Bcl-2 to exert its protective effect. Regulating expression of specific members of the Bcl-2 family by targeted gene expression is another potential therapeutic tool. This approach is covered in Chapter 11. 

Microcarrier-bound hRPE cells (dose estimated as 1000 cells per 150 microcarriers) produced a significant reduction in apomor-pliine-induced circling when implanted into the homo lateral striatum of 6-OHDA-lesioned Sprague-Dawley rats. This effect was achieved without immunosuppression and was sustained for the duration of the 18-week study. Unattached hRPE cells produced only a transient effect. 

To get further insights into the anti-CD3-induced nephrotoxicity, we investigated in a murine model the abihty of anti-CD3 mAb to directly damage native kidneys. For this purpose, we injected mice with the hamster anti-mouse CD3 mAb 145-2C11 [153]. Like OKT3, this mAb is immunosuppressive [154] and first induces a transient release of several cytokines in the circulation, such as IL-2, IL-6, TNF-a, and IFN-y [102, 155, 156]. Histologic analysis revealed signs of tubular ne-... 

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