Patent US6180355

41 Pages·2013·3.18 MB·English

US006180355B1
(12) United States Patent (10) Patent N0.: US 6,180,355 B1
Alexander et al. (45) Date of Patent: Jan. 30, 2001
(54) METHOD FOR DIAGNOSING AND Ryoji Yasumoto et al., “Seminal Plasma Cytokines in Non
TREATING CHRONIC PELVIC PAIN bacterial Prostatitis: Changes FolloWing Spar?oxacin Treat
SYNDROME ment,” Acta Urol. Jpn., 1995, 41: pp.771—774.
F. Comhaire et al., “Cytokines in Semen of Normal Men and
(75) Inventors: Richard B. Alexander; Sathibalan
of Patients With Andrological Diseases,” American Journal
Ponniah, both of Ellicott City, MD
of Reproductive Immunology, 1994, 1994, 31: pp. 99—103.
(Us)
Kouichiro Shimoya et al., “Detection of Monocyte Chemo
(73) Assignee: University of Maryland, Baltimore, tactic and Activating Factor (MCAF) and Interleukin (IL)—6
Baltimore, MD (US) in Human Seminal Plasma and Effect of Leukospermia on
These Cytokine Levels,” American Journal of Reproductive
( * ) Notice: Under 35 U.S.C. 154(b), the term of this Immunology, 1995, 34: pp. 311—316.
patent shall be extended for 0 days.
Taiji Nishimura et al., IL—1ra Versus IL—1 Levels in Pros
tatic Fluid from Prostatitis Patients, Urol Int 1998, 60: pp.
(21) Appl. No.: 09/306,927
92—96.
(22) Filed: May 7, 1999 Taiji Nishimura et al., “LoW Levels of IL—1ra Versus IL—1
Levels in Prostatic Fluid Are Not a Cause of Prolongation of
Related US. Application Data
Prostatitis,” J. Nippon Med. Sch., 1996, 63 (6): pp. 62—63.
(60) Provisional application No. 60/084,668, ?led on May 7,
1998. Maryann Nocera and T. Ming Chu, “Characterization of
Latent Transforming GroWth Factor—[3 From Human Semi
(51) Int. Cl.7 ......................... .. G01N 33/50; G01N 33/53 nal Plasma,” American Journal of Reproductive Immunol
ogy, 1995, 33: pp. 282—291.
(52) US. Cl. ............................................. .. 435/71; 435/78
(List continued on next page.)
(58) Field of Search .......................... .. 435/7.1, 7.8, 7.92,
435/794; 424/141, 145.1, 158.1; 436/501, Primary Examiner—Robert A. SchWartZman
86, 87 Assistant Examiner—Thomas G. Larson
(74) Attorney, Agent, or Firm—Steven J. Hultquist;
(56) References Cited
William A. Barrett
PUBLICATIONS
(57) ABSTRACT
Yasumoto et al. (1995) Seminal plasma cytokines in non
bacterial prostatitis: Changes following spar?oxacin treat The present invention provides a superior method of diag
ment. Acta Urologica J aponica 41: 771—774. (English nosing Chronic Pelvic Pain Syndrome in men comprising
abstract only, BIOSIS accession No. 1996: 70462).* measuring levels of cytokines in semen or components or
Depuydt et al. (1996) The relation betWeen reactive oxygen fractions of semen. The invention also provides a method of
species and cytokines in andrological patients With or With treating a condition associated With elevated levels of a
out male accessory gland infection. J. Andrology, 17: cytokine, such as TNF-(X, in semen or a component or
fraction thereof, comprising administering a therapeutically
699—707.*
NaZ et al. (1994) Increased levels of interleukin—6 in seminal effective amount of an ant-cytokine compound or
plasma of infertile men. J. Andrology 15: 220—227.* composition, such as an anti-TNF-ot compound or compo
R.B. Alexander, F. Brady and S. Ponnian, “Autoimmune sition.
Prostatitis: Evidence of T Cell Reactivity With Normal
Prostatic Proteins,” Urology, 50(6) pp. 893—899. 1997. 14 Claims, 8 Drawing Sheets
SEMINAL PLASMA GM-CSF LEVELS, pg/ml
PROSTATITIS N=8
NORMALS N=7
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US 6,180,355 B1
Page 2
PUBLICATIONS Brigitte Dousset et al., “Seminal Cytokine Concentrations
(IL—1[3, IL—2, IL—6, sR IL—2, sR IL—6), Semen Parameters
Maryann Nocera and T. Ming Chu, “Transforming Growth and Blood Hormonal Status in Male Infertility,” Human
Factor [3 as an Immunosuppressive Protein in Human Semi Reproduction, 1997, 12 (7): pp. 1476—1479.
nal Plasma,” American Journal of Reproductive Immunol Mahmoud Huleihel et al., “Distinct Expression of Cytokines
ogy, 1993, 30: pp. 1—8. and Mitogenic Inhibitory Factors in Semen of Fertile and
Bernadette Loras et al., “Seminal Transforming GroWth Infertile Men,” American Journal of Immunology, 1997, 37:
Factor—[3 in Normal and Infertile Men,” Human Reproduc
pp. 304—309.
tion, 1999, 14 (6): pp. 1534—1539.
Matthias S. GruschWitZ et al., “Cytokine Levels in the
Fiona C. Denison et al., “Seminal Plasma Components
Seminal Plasma of Infertile Males,” Journal of Andrology,
Stimulate Interleukin—8 and Interleukin—10 Release,”
Mar/Apr. 1996, 17 (2): pp. 158—163.
Molecular Human Reproduction, 1999, 5 (3):pp.220—226.
E. Koumantakis et al., “Increased Levels of Interleukin—8 in LaWrence F. BroWn et al., “Vascular Permeability Factor
Human Seminal Plasma,” Andrologia, 1998, 30: pp. (Vascular Endothelial GroWth Factor) Is Strongly Expressed
339—343. in the Normal Male Genital Tract and is Present in Substan
G. Frenette et al., “High Concentrations of the Macrophage tial Quantities in Semen,” The Journal of Urology, Aug.
Migration Inhibitory Factor in Human Seminal Plasma and 1995, 154: pp. 576—579.
Prostatic Tissues,” Archives of Andrology, 1998, 41: pp. R. Paradisi et al., “Interleukin—2 in Seminal Plasma of
185—193. Fertile and Infertile Men,” Archives of Andrology, 1995, 35:
Alexander E. Omu et al., “Antibiotic Therapy of Seminal pp. 35—41.
Infection Effect on Antioxidant Activity and T—Helper
Mahadevan Raj asekaran et al., “Oxidative Stress and Inter
Cytokines,” The Journal of Reproductive Medicine, 1998,
leukins in Seminal Plasma During Leukocytospermia,” Fer
43 (10): pp. 857—864.
tility and Sterility, Jul. 1995, 64 (1): pp. 166—171.
I. Matalliotakis et al., “Cytokine Levels in Seminal Plama,”
Clin. Exp. Obst. & Gyn., 1998, 25 (1—2): pp. 58—60. Rajesh K. NaZ and Paul Kaplan, “Increased Levels of
I. Matalliotakis et al., “Interleukin—6 in Seminal Plasma of Interleukin—6 in Seminal Plasma of Infertile Men,” Journal
Fertile and Infertile Men,” Archives of Andrology, 1998, 41: of Andrology, May/Jun. 1994, 15 (3): pp. 220—227.
pp. 43—50. S. ShimonovitZ et al., “High Concentration of Soluble
Rajesh K. NaZ and Lori Evans, “Presence and Modulation of Interleukin—2 Receptors in Ejaculate With LoW Sperm
Interleukin—12 in Seminal Plasma of Fertile and Infertile Motility,” Human Reproduction, 1994, 9 (4): pp. 653—655.
Men,” Journal of Andrology, 1998, 19 (3): pp. 302—307.
Nina—Beate Liabakk et al., “High Concentrations of the
M. FujisaWa et al., “Levels of Interferon 0t and y in Seminal
Soluble p55 Tumour Necrosis Factor Receptor in Human
Plasma of NormoZoospermic, OligoZoospermic, and
Seminal Plasma,” Human Reproduction, 1993, 8 (11): pp.
AZoospermic Men,” Archives of Andrology, 1998, 40: pp.
1837—1842.
211—214.
Y. Hirata et al., “Epidermal GroWth Factor in Human
D.J. Anderson et al., “Quantitation of Mediators of In?am
mation and Immunity in Genital Tract Secretions and Their Seminal Plasma,” Horm. Metabol. Res., 1987, 19: pp.
35—37.
Relevance to HIV Type 1 Transmission,” AIDS Research
and Human Retroviruses, 1998, 14 (Supplement 1): pp. Roger D. Kempers, “Distinct Expression Levels of Cytok
S43—S49. ines and Soluble Cytokine Receptors in Seminal Plasma of
Roberto Paradisi et al., “T—Helper 2 Type Cytokine and Fertile and Infertile Men,” Fertility and Sterility, Jul. 1996,
Soluble Interleukin—2 Receptor Levels in Seminal Plasma of 66(1): pp. 135—139.
Infertile Men,” American Journal of Reproductive Immu
nology, 1997, 38: pp. 94—99. * cited by examiner
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