Interleukin adverse effects

Also when the cytokine interleukin 2 (IL-2) was used for cancer treatment, serious adverse effects were noted resulting in the so-called vascular leak syndrome (VLS) [98, 99]. VLS is a life-threatening toxicity marked by vasopermeability with hypotension induced during high dose IL-2 treatment of cancer patients [100]. VLS is caused by endothelial activation and can be induced in lungs and liver of mice by IL2 administration [99]. The mechanism of IL-2-induced VLS is still poorly understood and at present there is no specific therapy for VLS. For the investigation of these... 

Aldesleukin is with recombinant technology prepared interleukin-2 (IL-2). IL-2 binds to the IL-2 receptor and so stimulates proliferation of T-helper cells and cytotoxic T-cells. It also activates macrophages and stimulates B-cell activity. It is used in metastasized renal carcinoma. Life threatening car-diotoxicity may occur. Other adverse effects include bone marrow depression and neurotoxicity with manifestations varying from somnolence to delirium. 

The most common side effects of interleukin-11 are fatigue, headache, dizziness, and cardiovascular effects. The cardiovascular effects include anemia (due to hemodilution), dyspnea (due to fluid accumulation in the lungs), and transient atrial arrhythmias. Hypokalemia has also been seen in some patients. All of these adverse effects appear to be reversible. In the limited clinical trial data available thus far, recombinant thrombopoietin appears to be well tolerated. 

Anakinra is an interleukin-1 receptor antagonist. It has been used to treat rheumatoid arthritis (1,2). It has been tried in graft-versus-host disease, but without success (3). According to published trial data, moderate injection site reactions were the primary adverse effect and required treatment withdrawal in under 5% of patients. An erythematous rash was seldom observed. Although a few patients have developed antibodies to anakinra, these have not so far been associated with lack of efficacy or allergic skin reactions. 

Daclizumab, a humanized antibody directed against the alfa chain of the interleukin-2 receptor, has been used for initial immunosuppression in transplant patients. In a phase III trial in 275 patients who received ciclosporin, glucocorticoids, and daclizumab or placebo, there were no specific adverse effects associated with daclizumab (1). In particular, the cjhokine-release sjmdrome did not occur, and there was no difference in the incidence of fungal or cjhomega-lovirus infections between the two groups. 

Interleukin-10 is a potent anti-inflammatory and immunosuppressive cytokine with beneficial effects expected in a wide range of diseases (1). In healthy volunteers, its adverse effect profile mostly consisted of flu-like symptoms at the highest dose (SEDA-20, 336). First-degree atrioventricular block was noted in a few patients. Due to immunomodulating properties, potential adverse immunological effects, namely an increased risk of infections, autoimmune disorders, or B cell lymphoprolifera-tive disorders, can be anticipated. 

Interleukin-12, an immunomodulatory cytokine, has potential effects in several cancer and infectious diseases. Although interleukin-12 was considered to be reasonably safe in early clinical trials, severe and sometimes fatal multiple organ adverse effects have been described in subsequent studies (SEDA-20, 336). This unexpected profile of toxicity was later shown to result from schedule-dependent toxicity, which occurred only in patients with cancer who received multiple high doses without an initial single dose of interleukin-12 (1). This severe toxicity has since been avoided. 

IX 207-887 (10-methoxy-4//-benzo-(4,5)-cyclohepta-(l,2-6)-thiophene-4 ylidene acetic acid) is a slow-acting drug for use in rheumatoid arthritis. Its mechanism of action involves inhibition of the release of interleukin-1. Adverse effects have occurred in 22% of cases, most... 

Tacrolimus, a macrolide derivative, has similar immunosuppressive properties to ciclosporin and has effects on T lymphocytes by inhibiting interleukin-2 production. On a weight basis, tacrolimus is about 100 times more potent than ciclosporin. In view of the outcome of several multicenter trials, it has been used as an alternative to ciclosporin as a baseline regimen for the prophylaxis of renal and liver transplant rejection and in the treatment of acute rejection (SED-13,1130) (SEDA-21, 390) (1). The clinical pharmacology, clinical use, and adverse effects profile of tacrolimus in organ transplantation have been extensively reviewed (2). 

To find out if the concurrent use of trimetazidine and ciclosporin was associated with any adverse effects, 12 kidney transplant patients taking ciclosporin were given trimetazidine 40 mg twice daily for 5 days. No changes in the pharmacokinetics of the ciclosporin were seen, and there were no alterations in interleukin-2 concentrations or soluble interleukin-2 receptors. An associated study by the same group of workers using two models (the lymphoproliferative response of normal human lymphocytes to phytohaemagglutinin and a delayed mouse hypersensitivity model) similarly found that trimetazidine did not interfere with the effects of ciclosporin. It was concluded on the basis of these two studies that the concurrent use of ciclosporin and trimetazidine need not be avoided. 

Similarly, in transgenic mice carrying the human interleukin-3 (IL-3) a or Pc receptor, these receptors are expressed not only in bone marrow cells, but also in the brain (pc receptor) and testis (a and Pc receptors) of the transgenic mice. Whether or not such expression is physiological is not yet known nevertheless these findings in transgenic mice may provide information about possible adverse effects in humans. 

Ryffel B (1997). Interleukin-12 Role of interferon-gamma in IL-12 adverse effects. Clinical Immunology and Immunopathology, 83 18-20. 

Imiquimod (Aldara) is an immunomodulator approved for the treatment of external genital and perianal warts in adults. The precise mechanism of its action is not fully understood but is thought to be related to imiquimod s ability to stimulate peripheral mononuclear cells to release interferon- and to stimulate macrophages to produce interleukins-1, -6, -8, and tumor necrosis factor-. Imiquimod should be applied to the wart tissue 3 times per week and left on the skin for 6-10 hours prior to washing off with mild soap and water. Treatment should be continued until eradication of the warts is accomplished, but not for more than a total of 16 weeks. Percutaneous absorption is minimal, with less than 0.9% absorbed following a single-dose application. Adverse side effects consist of local inflammatory reactions, including pruritus, erythema, and superficial erosion. 

Hydroquinone has been extensively studied. Carbonnelle et al. (1995) have investigated the effect of hydroquinone on IL-1 release from human monocytes, in an effort to show that reduced interleukin release my inhibit cytokine release by monocytes, thereby adversely affecting the regulation of hematopoiesis. Support for this mechanism comes from the work of Miller et al. (1994) who showed that hydroquinone decreased the enzyme responsible for the conversion of interleukin precursors in murine bone marrow macrophages. In addition, hydroquinone has been shown to alter differentiation of myeloid progenitor cells which may be important to benzene leukemogenesis (Irons and Stillman 1993 Irons et al. 1992). 

---