Objectives: To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis ( RA).Methods: Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass index. Concentrations of glucose, adrenocorticotropic hormone ( ACTH), cortisol, Delta4-androstenedione (ASD), dehydroepiandrosterone ( DHEA), dehydroepiandrosterone sulphate (DHEAS), 17alpha-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 6 (IL6), and tumour necrosis factor alpha (TNFalpha) were analysed in plasma.Results: Patients had comparable responses of glucose, cortisol, ACTH, ASD, and 17OHP to hypoglycaemia, without any signs of hypothalamic insufficiency. Patients had lower basal DHEAS than controls (3.03 (0.37) mumol/l v 5.1 (0.9) mumol/l, respectively; p<0.05); borderline lower basal DHEA levels (p=0.067); while the response of DHEA to hypoglycaemia was comparable to that of controls. Patients with RA had lower EPI (p=0.005) and NE (p<0.001) responses to hypoglycaemia. TNFalpha and IL6 were higher (p<0.05) in patients with RA (TNF alpha 8 (2.8) pg/ml in RA v 1.1 (0.5) pg/ml in controls and IL6 15.1 (6.7) pg/ml v 1.4 (0.7) pg/ml).Conclusions: Lower basal DHEAS levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA.

OBJECTIVE:Prolactin (PRL) and growth hormone (GH) are pituitary hormones with immunomodulating properties. Their upregulated secretion may play a role in the pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS).METHODS:Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) were analyzed.RESULTS:RA patients had significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA controls. During hypoglycemia double or higher increase of plasma PRL occurred in 5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model procedure, no significant differences in PRL or GH responses were observed in patients with RA and AS. TNF-a was higher in patients with RA compared to RA controls (p < 0.05). There was no significant difference in TNF-a concentrations between AS patients and AS controls. IL-6 was higher in RA patients compared to controls (p < 0.05) and in AS patients compared to controls (p < 0.01). Significant positive correlation was found between TNF-a levels and AUC of PRL in AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA patients.CONCLUSION:Our results indicate no upregulated PRL or GH responses to stimulation in premenopausal women with RA or men with AS.

An open 18-week study with a preparation of cyclosporin administered to patients with psoriatic arthritis confirmed the therapeutic efficacy of the preparation. Given the low frequency of adverse effects (at the initial and maintenance daily dose), the preparation could also be considered relatively safe. A pronounced improvement in psoriatic symptoms was observed during the study. As early as 2 weeks after administration of an average daily dose of cyclosporin A of 4.8 mg/kg, skin symptoms improved by 65.5%. The most intense effect on the activity of arthritis was observed after 18 weeks. The lowest optimal effective maintenance dose was 3.26 mg/kg/day. Improvement was achieved after an average of 10 weeks' cyclosporin administration.

Cyclosporin A was administered in the dosage of 3.5 mg/kg/day to nine patients with,systemic: lupus erythematosus (SLE) and lupus nephritis refractory to cyclophosphamide or azathioprine treatment, or adverse effects of these drugs. The patients received cyclosporin A over a period of at least 24 months. The clinical activity of SLE, assessed according to the SLE clinical activity score (ECLAM) criteria, decreased in eight out of the nine patients in the series. Suppression of lupus nephritis with significantly diminished proteinuria (p<0.001) was recorded in eight patients. The increased values of antibodies to double-stranded deoxyribonucleic acid found in six patients became normalized, similar to the antibodies to deoxyribonucleoprotein in four out of six patients, and complement values increased in five of six patients. After suppression of SLE activity, the daily dosage of corticosteroids could be reduced in seven out of nine patients and the cyclosporin A dosage in eight out of nine patients. Due to the development of nephrotoxicity, cyclosporin A therapy had to be withdrawn in one patient after 10 months and in a further one after 24 months. The other side effects (hypertrichosis, gingival hyperplasia, hypertension) did not necessitate cessation of cyclosporin A treatment. In the daily dosage of 3.5 mg/kg, cyclosporin A was found to be effective in suppressing of the clinical and immunological activity of SLE and lupus nephritis. It can be administered over a period of more than one year, yet its long-term use requires careful monitoring, particularly with regard to the risk of nephrotoxicity development.

After oral administration of a combination of hydrolytic enzymes (Wobenzym(R)) the leukocyte system of healthy subjects and patients with rheumatoid arthritis (RA) responds to ConA and NDV in vitro through a different pattern of IFN-gamma and IFN-alpha production, respectively in healthy subjects, after Wobenzym(R) medication the IFN-gamma as well as the IFN-alpha producing ability was increased. This cell system was not able to release a detectable level of IFN-gamma spontaneously and trypsin itself had no IFN-inducing ability. RA patients with defi cient producing ability of leukocytes to ConA failed to be restored in IFN producing capacity by the enzyme preparation and were even more decreased in the production of IFN-gamma after enzyme treatment. Wobenzym(R) treatment of healthy volunteers reduced TGF-beta 1 concentration in their plasma. in contrast to these results, whole blood cells of these volunteers produced TGF-beta 1 spontaneously.

The association of SLE with tuberculosis (TB) was studied in a group of 388 patients with SLE monitored between 1953-1994. TB was diagnosed in 14 patients (3.6%). The occurrence of septic fevers in SLE patients that did not respond to glucocorticoid therapy indicated the possibility of complication with TB. SLE-associated TB included miliary and far-advanced pulmonary and extrapulmonary forms. Three patients from our group died due to myco-bacterial infection and one patient died of active SLE and TB. The treatment was successful in nine patients. Early diagnosis and appropriate management are mandatory in SLE associated TB, which otherwise may have a potentially fatal outcome.

The paper presents general therapeutic principles applied in systemic vasculitis. Several factors may help to contain the clinical activity, such as the location and extent of the inflammatory process affecting the vascular system, the ultimate narrowing of the vascular lumen with subsequent ischemia of the affected tissue and organ. Treatment of vasculitis involves besides glucocorticoids not only cytotoxic drugs (cyclophosphamide, chlorambucil, methotrexate), and immunomodulatory therapeutic agents with immunosuppressive action (cyclosporin A) but also other immunomodulatory drugs, as e.g. dialyzed homogenate of leukocytes (DHL), pentoxyphylline, hydrolytic enzymes, and monoclonal antibodies. The authors emphasize the importance of a complex approach in the management of systemic vasculitis. (Tab. 1, Ref. 36.).

The authors review recent findings pertaining to the pathogenesis of systemic lupus erythematosus. It was revealed that knowledge of impaired humoral and cellular immunity is of great practical importance and substantially improves the prognosis of the disease.