The effects of interleukin-4 and lipopolysaccharide on CRH-41 release from acute rat hypothalamic explants

Pharmacological

I23

Research, Vbl. 26, Supplement I, 1992

THE EFFECTS OF INTERLEUKIN-4 AND LIPOPOLYSACCHARIDEON CRH41 RELEASE FROM ACUTE RAT HYPOTHALAMICEXPLANTS G. Pozzoli, E. Ragazzoni, P. Navarra and P. Preziosi Dept. of Pharmacology, Catholic University Medical School, Rome, Italy. It is known that cytokines such as IL-l and IL-6 can acutely level, and stimulate the release of CRH-41 at hypothalamic thus activate the hypothalamo-pituitary-adrenal axis !HPA). In this study we investigated the effect exerted by another interleukin-4 (IL-4) on CRH-41 release from such cytokine, rat hypothalamic explants. Furthermore, since the in vitro available IL-4 preparation contained bacterial lipopolysacof the HPA, we sought charide !LPS), a well-known activator the direct effect of LPS on CRH-41 release. IL-4 was unable to stimulate CRH-41 release in 20 min incubation in the dose-range l-100 rig/ml; similarly LPS, O.Oldid not affect CRH-41 release in 20 min experi10 w/ml, ments. In 1 hour experiments, LPS produced a dose-dependent decrease of CRH-41 compared to control. It is concluded that IL-4 does not share with IL-1 and IL-6 the ability to stimulate directly CRH-41 release in vitro. The ability of LPS to activate the HPA in vivo seems to a direct effect on CRH-41 release. not to be related Supported by CNR grants 90.03213.CT04 and 91.00438.CT04

COMBINATION

THERAPIES

WITH

AND CLINICAL APPLICATIONS Cartesio Fawalli, Antonio Dept.

of

Rome,

Italy.

Our

Exp.

Medicine

experimental

interferon

animal

(IFN),

significantly

when

treated

models,

as well as pre-treatment

IL-Z,

inducing

or

B-16,

an

HORMONES

Mastino,

Enrico

Bioch.

Sciences,

studies

in

killer

AND

CYTOKINES:

RATIONAL

BASIS

Rome"Tor

Vergata"

Garaci

demonstrated

administered

restoring natural

(CY)

that

and

THYMIC

University that

combination, (NK)

of thymosin

a-l

were

activity

in

(TAl)

effective

and in

cyclophosphamide-

or Friend leukemia cell (FLC) experimental tumor controlling tumor growth. More recently we have found TAl in vitro or in vivo potentiates the effect of 3LL

in with

enhancement

of

cytotoxic

activity

in

spleen

cells

from

normal as well as from tumor and/or CY suppressed mice. Combined chemoimmunotherapy using TAl and IL-Z after CY was also very effective in controlling tumor growth. The general picture suggests that TAl commit immune effector cell precursors and regulate a program of development, by optimalising their targetting by IFN, IL-Z, and probably other cytokines. Thus it is rational the use of TAl in combination with other cytokines in order to obtain maximum efficacy. Our research group is now engaged in basic and clinical experimental studies using thymic hormones in combination with other cytokines in order to develop therapeutic protocols for cancer and infectius diseases.