Presence of INFg-secreting lymphocytes specific to prostate antigens
in a group of chronic prostatitis patients
Ruben Dario Motrich
a
, Mariana Maccioni
a
, Rosa Molina
b
, Andrea Tissera
b
, Jose´ Olmedo
c
,
Clelia Marı´a Riera
a
, Virginia Elena Rivero
a,
*
a
Centro de Investigaciones en Bioquı´mica Clı´nica e Inmunologı´a (CIBICI-CONICET), Departamento de Bioquı´mica Clı´nica, Facultad de Ciencias
Quı´micas, Universidad Nacional de Co´rdoba, Haya de la Torre esquina Medina Allende. Ciudad Universitaria, Co´rdoba 5000, Argentina
b
LAR, Laboratorio de Andrologı´a y Reproduccio´n, Co´rdoba, Argentina
c
FUCDIM, Fundacio´ n Urolo´ gica Co´rdoba para la Docencia e Investigacio´n Me´dica, Co´rdoba, Argentina
Received 24 February 2005; accepted with revision 15 March 2005
Available online 25 April 2005
Abstract
Acute and chronic infectious prostatitis are the best understood of the prostate syndromes, but they are the least frequent. In contrast,
although chronic non-infectious prostatitis is the most frequent syndrome, its cause has proved elusive despite years of investigation. In the
present study, we analyzed a group of patients with infectious and non-infectious chronic prostatitis in order to search for the presence of a
possible autoimmune response to prostate antigens. We demonstrated the presence of lymphocytes able to proliferate in response to known
human prostate antigens such as PSA and PAP only in a group of patients with non-infectious chronic prostatitis. We observed that, as in other
autoimmune diseases, a proliferative response against two or more autoantigens was a common feature. Moreover, when INFg and IL-10
levels were measured in culture supernatants, significantly elevated levels of INFg were detected only in samples from patients with positive
proliferative response to prostate antigens. Interestingly, only these patients showed significantly elevated levels of inflammatory cytokines
(IL-1 and TNF-a) in seminal plasma, arguing for a local inflammation of non-infectious cause. Our results show that INFg-secreting
lymphocytes specific to prostate antigens are in fact detected in 34% of the patients with chronic non-infectious prostatitis. We speculate that
these cells could be involved in the inflammatory process taking place in the prostate gland and therefore could alter its biological function.
D 2005 Elsevier Inc. All rights reserved.
Keywords: Chronic pelvic pain syndrome; INFg; Autoimmunity
Introduction
Epidemiological research during the past decade has indi-
cated ‘‘prostatitis’’ to be one of the major medical healthcare
problems in urology [1]. NIH proposed a classification of
prostatitis syndromes in four categories [2]. Acute and
chronic bacterial prostatitis (categories I and II), chronic
pelvic pain syndrome (CPPS) (category III) and asympto-
matic inflammatory prostatitis (category IV). The major new
category, CPPS, is divided in CPPS-inflammatory and CPPS
non-inflammatory and encompasses the former chronic non-
bacterial prostatitis and prostatodynia respectively [3].Itis
defined as otherwise unexplained genital or pelvic pain (in
around the penis, perineum and scrotum) in males of at least
age 18, lasting for at least 3 months. The distinction between
inflammatory and non-inflammatory CPPS is based on the
finding of leukocytes in semen, in expressed prostate
secretions (EPS) or in the urine after prostate massage [4].
Although acute and chronic bacterial prostatitis are the
best understood of these prostatic syndromes, they are the
least frequent [5]. Typically, the causative pathogen is easily
detected in semen, EPS or in urine after prostatic massage,
and then the appropriate therapy can be indicated. In contrast,
the cause of CPPS has proved elusive despite years of
investigation [6]. Many investigators support the hypothesis
that non-classically culturable microorganisms could be
playing a role in the pathogenesis of this syndrome. Some
1521-6616/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.clim.2005.03.011
* Corresponding author. Fax: +54 351 4333048.
E-mail address: vrivero@bioclin.fcq.unc.edu.ar (V.E. Rivero).
Clinical Immunology 116 (2005) 149 – 157
www.elsevier.com/locate/yclim