[Safety of immunosuppressants]. / Sicherheit der Immunsuppressiva.

METABOLISM: Cyclosporin A and leflunomide may increase the blood pressure, whereas administration of prednisolone and tacrolimus may cause hyperglycemia. Azathioprine, chloroquine, methotrexate and mycophenolate mofetil seem to be metabolically neutral. Tocilizumab and tumor necrosis factor (TNF) alpha blockers have a negative effect on the lipid profile. INFECTIONS: The overall infection risk for prednisolone is estimated to be 1.3. This risk for methotrexate is also 1.3 compared to other disease modifying antirheumatic drugs (DMARDs). Regarding biologics, the highest risk of serious infections was associated with certolizumab pegol and tocilizumab, in contrast to abatacept and rituximab which showed the lowest risk. CANCER RISK: Azathioprine and cyclosporin A are associated with a markedly increased risk of non-melanoma skin cancer. According to the RABBIT registry no significant increase in tumor rate has been reported for biologics. PREGNANCY: Azathioprine, chloroquine, cyclosporin A, prednisolone, sulfasalazine, tacrolimus and cyclophosphamide (only after the second trimester) may be administered during pregnancy. Biologics should be avoided unless there is a treatment need in cases of uncontrolled disease activity. BREAST FEEDING: Only chloroquine, prednisolone, sulfasalazine and tacrolimus may be taken during breast feeding. There are insufficient data on the safety of biologics.

Cytokine gene expression in regenerating haematopoietic tissues of mice after cyclophosphamide treatment.

The goal of the study was to investigate changes in expression of selected growth factors tentatively involved in regeneration of haematopoietic tissues (bone marrow and spleen) following cyclophosphamide (CY) damage in the mouse. The bone marrow (BM) and spleen were examined separately, since the regenerating pattern for haematopoietic progenitor cells (HPC) markedly differs in these two haematopoietically active organs after CY. Cytokines assumed to have a stimulatory effect on HPC - stem cell factor (SCF), fetal liver tyrosine kinase 3-ligand (flt3-ligand), thrombopoietin (TPO), stromal cell-derived factor 1 (SDF-1), oncostatin M (OSM) -, a suppressive effect on HPC proliferation - macrophage inflammatory protein-1alpha (MIP-1alpha), transforming growth factor-beta1 (TGFbeta1), tumour necrosis factor-alpha (TNFalpha) - and to be involved in migration of HPC (SCF, flt3-ligand, MIP1alpha, SDF-1) were examined at the level of mRNA expression by means of real-time RT-PCR. The expression of a particular cytokine appears to be similar in both BM and spleen of untreated mice. CY administration changed the expression pattern of the studied genes in BM and spleen. In BM, the levels of mRNAs for SCF and SDF-1 were increased and that for TGFbeta1 decreased at time intervals at which HPC are known to proliferate intensively during BM regeneration. In contrast, stimulated proliferation of HPC in spleen was accompanied by increased expression of flt3-ligand and oncostatin M. Upon mobilization of HPC from BM into blood after CY, the expression of SCF, TPO, SDF-1 and TGFbeta1 tends to decrease in BM. Accumulation of HPC in spleen is accompanied by increased mRNA for flt3-ligand and OSM. Our findings demonstrate that different cytokines may be involved in the proliferation and mobilization/homing of HPC during recovery after CY damage in BM and spleen.

[Stromal cell-derived factor 1 (SDF-1). Its structure and function]. / Stromal cell-derived factor 1 (SDF-1). Jeho struktura a funkce.

SDF-1, a novel cytokine from alpha-chemokine family, plays a key role in regulation of haematopoiesis. It exists in two forms (alpha and beta) that originate from alternative splicing. Its high expression in the bone marrow microenvironment accounts for the release of progenitor cells in the circulation and represents a prevention of uncontrolled leak of CD34+ cells. Notably significant is its stimulation of proliferation of B-lineage progenitors, in other haematopoietic lineages it functions as a facilitating factor of other cytokines. Ability of induction of platelet aggregation reveals the role of SDF-1 in thrombogenesis and vascular lumen obliteration in vessels affected by atherosclerosis. The only receptor for SDF-1 is CXCR4, whose presence was proved in great numbers of tissues and organs. Their presence was also verified in brain tumours, whereas degree of their expression raises with grading, angiogenesis and occurrence of necrotic changes in tumour. Thanks to this feature it will probably be possible to estimate the prognosis of the patients. SDF-1 is also a suppressor of immune response via its facilitating activity on the interaction of the macrophages and CD8+ T lymphocytes. Affinity of the T-lymphocytotropic HIV to CXCR4 holds out hopes for a possible modulation of the infection with SDF-1. The significance of SDF-1 and its receptor CXCR4 is supported by morphological and functional abnormalities of new-born mice in their absence, especially disorders in haematopoiesis, angiogenesis and development of cardiac and nervous tissues.