Volume 7, Issue 3

In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

The basic pharmacokinetic parameters of MTX administered as monotherapy as well as in the combined therapy with simultaneous and prior administation of FU were investigated. The parameters were determined in the two-compartment open system on the basis of measurement of MTX levels in mice after i.p. administration of a single dose 20 mg/ kg of the drug. The FU dose was 20 mg/kg, too. The effect of the circadian rhythm on the kinetics of MTX have been taken into consideration. In one series of experiments the drugs were administered in the morning and in the other during midday hours . The statistical analysis of the obtained results showed the essential effect of the administration time on the pharmacokinetic parameters of MTX in mice. The statistical significal differences could be found: C max, AUC, CL, T 0,5 . The differences in T 0,5 , parameter resulting from coadministration of FU with the same circadian rhythm of MTX administration have been observed.

Serial urinary neopterin :creatinine ratios of 58 healthy adult sub jects were measured from 2 days prior to and up to 12 days post vaccination. An increase in the urinary neopterin of at least twice the baseline was detected in 24/ 46 subjects who received either a Mantoux skin test or a live viral vaccine (cell mediated immune group, median average increase above baseline = 206% (interquartile range 150-338% ) , and 'in 5/12 who received non-live vaccines known to stimulate mainly humoral immunity (humoral immune group, median average increase above baseline = 165%( (interquartile range 142-412%) ). The peaks in the urinary neopterin in the cell mediated group occurred between days 5 and 10 post-vaccination, with the mode on day 5. In contrast the 5 subjects in the humoral immune group all developed their peaks on day 7 or 8 . Three of these subjects received an influenza vaccine, one a typhoid vaccine and one a tetanus toxoid. No association was found between local or systemic side-effects of vaccination and raised urinary neopterin . In conclusion, the monitoring of urinary neopterin excretion in adults is sensitive enough to detect an immunological response to vaccination with immunogens that induce either cell mediated or humoral immune responses.