~

UNIVERSITY
BERKELEY DAVIS

OF CALIFORNIA,
IRVINE . LOS ANGELES

LOS ANGELES
RIVERSIDE SAN DIEGO SAN FRANCISCO SANTA BARBARA

UCLA
SANTA CRUZ

Center for Interdisciplinary Research in Immunology and Disease (CIRID)

DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY UCLA SCHOOL OF MEDICINE CENTER FOR THE HEALTH SCIENCES 10833 LE CONTE AVENUE LOS ANGELES, CAUFORNIA 900951747

August 6, 1997 Henry J. Heimlich, M.D., Sc.D. President The Heimlich Institute 2368 Victory Parkway, Suite 410 Cincinnati, OH 45206 Dear Henry:

(310) 825~6.~68. ~
(310) 206- 1318 (FAX)

Enclosed are tables of the data obtained on the samples provided by Chen Xiao Ping. We have problems with interpretation because of uncertainty as to when the samples were obtained in relation to therapy in most of the patients. Hopefully, you have more exact data. Chen Xiao Ping gave us shifting information at different times during his stay here. Patients 4003 and 4004 are probably the clearest. Presumably, the first samples were obtained before malariotherapy, the second samples during malariotherapy and the subsequent samples were after malariotherapy. 4003 had a baseline neopterin of 6.97 (within the normal range). P2M was normal and sTNF-RII was at the upper end of normal. A marked rise is seen about 3 weeks later during therapy. About 11 days later, there is substantial subsidence. Subsequently, values are in the normal range (but gradually falling) in 1994 and progressive increases in 1995 and 1996 until abnormal levels are recorded 9/11/96. Patient ID 4004 follows a similar course with the exception that his baseline was elevated in 1993. His post therapy values were generally below baseline and were mostly in the normal range in 1995 but were increased again in the 1996 sample. The other patients present the problems of not knowing if the first values were pre-treatment or were obtained during or soon after malariotherapy. The absence of certainty about these first values (Do they represent just disease or disease plus malariotherapy or disease plus some other infection?) presents difficulties for interpretation of the subsequent values,

In the accompanying graphs, please understand that the "0" time point only indicates the first sample that we had for patients 4001, 4002, 4005, 4006, 4007 and 4008. We are uncertain about their relationship to malariotherapy. Please feel free to use this data in reports and publications. We would appreciate an acknowledgment and credit to the support provided by NIH grants TW 00003 and AI 36086. The difficulties outlined above contributed to our concern that Chen Xiao Ping have a carefully 'Written out experimental plan (in English and in Chinese) in advance of future malariotherapy studies. Both versions of the plan should be available to you (I would be glad to review these). As you know, I believe that malariotherapy may act by similar mechanisms to those operating in the 5-day continuous intravenous IL-2 treatments developed by Lane, Kovacs and their colleagues. Both malaria and IL-2 stimulate marked increases in all or almost all cytokines. IL-2 induces CD4 increases without reductions in viral load. That is why we have been concerned to help Chen Xiao Ping have accurate CD4 measurements. He still has to develop a working relationship with the persons who have a flow cytometer at his institution. Sincerely

John L. ahey, M.Do Director" CIRID at UCLA Chair, Clinical Immunology Committee, International Union of Immunological Societies (lUIS) JLP/dm