Biochemical host response to interferon-beta.
To assess influence of host response to interferon-beta (IFN-beta), on biochemical parameters, beta 2-microglobulin (beta 2-M) and neopterin were evaluated in 15 and 12 patients respectively before and 24 h after 1-46 X 10(6) IU intravenously (i.v.) IFN-beta given every other day. In 4 additional patients, both molecules were determined before and after 24, 48, 72, and 96 h of weekly IFN-beta injections. Serum beta2-M levels significantly increased 24 h after IFN-beta administration in the overall group of 15 patients treated with the alternate day schedule (p = 0.003) as well as in the group of patients treated with the weekly schedule (p = 0.00003). Maximum induction of beta 2-M was observed 24 h after a single weekly IFN-beta injection, but the levels of this protein 72 h after still remained significantly higher than baseline values (p = 0.001). This demonstrates the progressive accumulation of beta 2-M in the circulation produced by the continuous IFN administration. Nevertheless, in patients treated with both IFN treatment schedules, a clear correlation between the increments of beta 2-M and the IFN-beta doses was observed (p = 0.00002 and p = 0.0016 for the alternate day and the weekly schedule respectively). Furthermore the under curve area (AUC) of 48 h beta 2-M levels after IFN administration significantly rose (p less than 0.05) with increasing IFN doses in 4/6 patients. In spite of the accumulation of beta 2-M in the circulation, the overall serum values of this protein 24 h after each successive IFN-injection, in the 15 patients receiving the alternate-day treatment, were significantly higher than before the immediate preceding dose both in patients with initially normal and those with initially high base levels (p = 0.00055 and p = 0.011, respectively). As with beta 2-M, neopterin levels significantly rose during IFN treatment (p less than 0.05) in the group of patients as a whole. After single weekly IFN-beta injections, maximum induction of neopterin was observed 24 h after administration, then the levels of this molecule slowly declined towards the baseline levels, but 96 h after, its levels were still significantly elevated (p less than 0.00001). Neopterin induction was not related to IFN-beta doses, but the levels of this molecule both before and after IFN administration were correlated with an increase in the number of IFN injections (p = 0.0006 and p = 0.0009, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
Liberati
A M
AM
Clinica Medica I, Università degli Studi di Perugia, Italy.
Fizzotti
M
M
Proietti
M G
MG
Di Marzio
R
R
Schippa
M
M
Biscottini
B
B
Senatore
M
M
Berruto
P
P
Canali
S
S
Peretti
G
G
D000328:Adult; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood; D053583:Interleukin-1beta; D008223:Lymphoma / Q000628:therapy; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D019798:Neopterin; D010446:Peptide Fragments / Q000097:blood; D001613:beta 2-Microglobulin / Q000097:blood
D007370:Interferon Type I; D007375:Interleukin-1; D053583:Interleukin-1beta; D010446:Peptide Fragments; D001613:beta 2-Microglobulin; C052994:interleukin-1beta (163-171); D001708:Biopterins; D019798:Neopterin