IMMUNOSUPPRESSION BY FATTY ACIDS

254 may initially affect the ground substance surrounding the cells. I suggest that the cell membrane may be altered by solvents. In studies relating mortality-rates with environment it is most important to have diagnoses confirmed by necropsy. More than one type of tumour is sometimes found in the same patient. Fortunately, there were several necropsies in this study, though I would have felt much more comfortable in reporting the results if every death could have been followed by necropsy. In my view, unless necropsies are considered mandatory in such studies, we cannot accumulate the hard evidence required for corrective actions by Government and in-

dustry. Hospital of

some

unknown mechanism induced

taneous

remissions

or

relapses of the disease.

Department of Neurology, University of Helsinki,

J. JUNTUNEN K. SAINIO

SF-00290 Helsinki 29, Finland

IMMUNOSUPPRESSION BY FATTY ACIDS our studies on the effect of fatty the in-vitro response of lymphocyte preparations to phytohaemagglutinin (P.H.A.), we have examined the effect of heptadecanoic acid (C17:0) on lymphocytes from human blood and rat spleen; only traces of heptadecanoic acid are normally found in tissues. The methods for preparing the fatty acids and human lymphocytes were as outlined previously,’ using an acid/albumin

SIR,-In continuation of

Cecil

County, PIETRO U. CAPURRO

Elkton, Maryland 21921, U.S.A.

EFFECT OF ALCOHOL UPON SYMPTOMS OF POLYNEUROPATHY

report our observations on changes in symptoms in a patient with polyneuropathy who was given alcohol; we have found that many polyneuropathic patients constantly feel better after they have drunk small amounts of alcohol. A young woman with idiopathic polyneuropathy of recurrent type, was studied over a period of six months in respect of subjective sensations, clinical status, and electroneurography after periods of alcohol drinking and periods without alcohol. After the daily consumption of approximately 5 ml of pure alcohol (calculated from all alcohol-containing drinks), subjective symptoms were much relieved compared with those during the non-alcoholic periods. Although the clinical status of the patient did not change notably between examinations, muscular power did seem to improve after alcohol. The conduction velocities of the peripheral nerves were measured on two successive days; on the first day the patient had been without alcohol for a week, and on the second day she had imbibed alcohol during the previous evening. Surface electrodes were used for stimulation and recording. The results are shown in the table. The experiment was repeated within a month with another pair of recordings. In both experiments the conduction velocities were increased by a mean of 10% (P<0.01, paired t test) and the distal latencies of the motor responses were diminished by a mean of 10% (P<0.05) after alcohol intake. The skin temperatures were somewhat higher in the session, after drinking alcohol, but the changes in temperature do not explain the difference between the two recordings.’ After six months the patient was in significantly better condition. In this polyneuropathic patient there is a clear correlation between drinking alcohol and relief of subjective symptoms and improvements in electroneurographic findings and clinical

SIR,—We wish

on

IMMUNE INHIBITORY PROPERTIES OF FATTY ACIDS

to

All incubations contained P.H.A. Results are expressed as % of the no. of counts observed in comparable incubations in which the cells had been stimulated with P.H A., and which contained an equivalent amount of albumin to that added with the acids. The number of experiments is shown in italic type.

ratio of 2/1. The rat spleen cells were obtained by teasing the spleens and centrifuging the cells at 400g over ’Lymphoprep’ (Nyegaard, Oslo). The cells were incubated in round-bottomed tubes. 5x 105 human lymphocytes were incubated in minimum essential medium for 24 h with the appropriate additions, followed by an 18 h pulse of [2-’°C] uridine. For the rat cells 7 x 105 cells were incubated in RPMI 1640 for 48 h with or without the additions, followed by an 18 h pulse of [6-3H] thymidine. As shown in the table, heptadecanoic acid exerts potent inhibitory effects on the cells from both sources-indeed it is the most inhibitory of all the acids we have so far tested. These results, added to our earlier findings, emphasise that it is misleading2 to concentrate on polyunsaturated fatty acids in looking for effective inhibitors in this system. By widening the investigation to other acids, both naturally occurring and 1.

Weyman, C., Belin, J., Smith,

A. D.,

Thompson,

R. H. S.

Lancet, 1975, ii,

33. 1.

by

alcohol; it is difficult to explain by the direct effects of alcohol, by a placebo effect, by changed skin temperature, or by spon-

acids

Department of Laboratories, Union

This suggests

status.

Johnson, E. W., Olsen, K. J. J. Am.

med. Ass. 1960,

CONDUCTION

172, 2030.

2. Merlin, J.,

Hughes,

D. Int. Archs Allergy

appl.

Immun.

VELOCITIES, DISTAL LATENCIES, AND TEMPERATURE BEFORE AND AFTER DRINKING ALCOHOL

1975, 48, 203

255 the possibility of developing an effective means for suppressing the immune response in vivo may be increased.

synthetic,

Courtauld Institute of Biochemistry, Middlesex Hospital Medical School, London W1P 5PR

A. D. SMITH W. M. TSANG C. WEYMAN J. BELIN

VASOACTIVE INTESTINAL POLYPEPTIDE

SIR,—Dr Larsson (July 17, p. 149) has confirmed the findings of neural vasoactive intestinal polypeptide (v.i.p.) by our

group’

ference does exist, it seems, contrary to Godfrey’s finding, that the disease is more common in areas where parasitic infestations are rampant, and where ascariasis may reach a prevalence of 90-100% of all children. Furthermore, a common occurrence was the coexistence of both conditions in the same

patient. While we do not believe that a causal connection exists between parasitosis and asthma, there is also clearly no protective effect of the parasitosis either. If any relation does exist between the two conditions, it is a direct rather than an inverse one.

Nassr Pædiatric Hospital, Gaza (via Israel)

v.i.p.

is

v.i.p.

cells

can

be found in the gut mucosa.34Furthermore

v.i.p.-secreting apudomas are not of neural origin.4 The suggestion that diarrhoea may be caused by agents other than v.i.p. seems self-evident. Indeed, a third of gastrinoma patients have troublesome diarrhoea, and this feature is also seem in the glucagonoma syndromedespite normal v.i.p. and in many cases normal pancreatic polypeptide (P.P.) levels.6 It is possible that P.P. may be associated with diarrhoea, though many patients with high plasma-p.p. values (e.g., with insulinomas) have no diarrhoea.6 We are studying a patient with diarrhoea, normal v.i.p., and high plasma-p.p. produced by hepatic metastases of a pancreatic P.P.-oma, and it is indeed possible that P.P. is responsible for the clinical symptoms. That v.i.p. is responsible for diarrhoea of v.i.p.-omas is incontrovertible. Infusions of v.i.p. in pigs producing similar blood levels result in severe diarrhcea.7 A third of pancreatic v.i.p.-omas

MACROPHAGES v. CANCER

most

with massive diarrhoea have absent tumour P.P. cells and normal plasma P.P. levels.6 Ganglioneuromas producing v.i.p. and 9 watery diarrhoea* are never associated with excess P.P. production. Departments of Histochemistry and Medicine, Royal Postgraduate Medical School, London W12

melanoma’ and with cancer of the prostate,2have emphasised the importance of macrophages in this form of immunotherapy. B.C.G. contact suppression of tumours is a hostmediated response since the organisms are not directly cyto-

cutaneous

toxic for

tumour

cells, but

treatment

is successful in animals

lacking full lymphocyte competence. Thus, B.C.G. contact therapy of syngeneically transplanted rat tumours is successful even in immunosuppressed animals,3 4 and rat tumours xenografted to athymic "nude" mice may be prevented from FACILITATION OF B.C.G. CONTACT SUPPRESSION OF HEPATOMA

D23

BY

SYNGENEIC MACROPHAGES

S. R. BLOOM A. G. EVERSON PEARSE

Strip. In Gaza asthma is an extremely common disease among both children and adults. While no exact figures exist concerning its incidence in the population, it is among the most frequent diagnoses made in the outpatient clinics and emergency room of our hospital, with a frequency reaching 10—20% of all children examined. In contrast with Godfrey’s findings, no significant difference in the incidence of the disease could be seen among children from city, village, or refugee camps. If any difM. G., Bloom, S. R., Polak, J. M., Albyquerque, R. H., Modlin, I., Pearse, A G. E. Lancet, 1976, i, 991. 2 Said, S I., Rosenberg, R. N. Science, 1976, 192, 907. 3. Polak, J. M., Pearse, A. G. E., Garaud, J.-C., Bloom, S. R. Gut, 1974, 15,

Bryant,

720. 4. Bloom, S

SIR,-Your editorial (July 3, p. 27) draws attention to the paucity of knowledge concerning the role of macrophages both in immunosurveillance and in immunotherapy of cancer. Recent results, from this and other laboratories, of investigations on the mechanism of action ofB.c.G. regionally applied to tumour deposits, such as has been well described clinically with

J. M. POLAK

IgE, PARASITES, AND ALLERGY SIR,—Iwas astonished to realise that a generalisation such as the one which appears in your editorial of April 24 (p. 894}-"there is evidence for an inverse relation between parasites and allergy: asthma and hay fever are rare in parts of the world where the population is heavily parasitised"-was based uniquely on the findings of Godfrey in the Gambia.’° While this may be true in the Gambia, it certainly is not in the Gaza

1.

E. E. LASCH

subsequently by Said and Rosenberg.2 However, not only a neural peptide, for numerous endocrine

and

R., Polak, J. M. in Gastrointestinal Hormones (edited by J. C. Thompson),p. 635. Austin, Texas, 1975. 5. Mallinson, C. M., Bloom, S. R., Warin, A. P., Salmon, P. R., Cox, B. Lancet, 1974, ii, 1. 6 Polak. J M , Bloom, S. R., Adrian, T. E., Heitz, Ph., Bryant, M. G., Pearse, A G. E. ibid. 1976, i, 328. 7 Bloom. S R., Mitchell, S. J., Modlin, I. (Unpublished). 8 Swift, P. G. F., Bloom, S. R., Harris, F. Archs Dis. Childh. 1975, 50, 896. 9 Bloom, S. R., Polak, J. M., Pearse, A. G. E. Lancet, 1973, ii, 14. 10 Godfrey. R C Clin. Allergy, 1975, 5, 201.

*Glaxo percutaneous

vaccine B.P., 3x10’ viable units/mg organisms, representing approximately 20% viability.

moist

weight

of

type of B.C.G. therapy.’ In contrast, treatment of animals with particulate silica, of a type known to be selectively toxic for macrophages, abrogates B.C.G.-mediated tumour contact suppression both in rats6 and athymic mice,6 indicating that macrophages play a primary and important role in this type of local therapy. Furthermore, whilst transplanted rat tumours normally contain a proportion of host macrophages, varying widely between tumour types, there is a distinct correlation between the maximum number of cells of each tumour that can be suppressed by contact with B.C.G. and the extent of its host macrophage infiltration.8 Thus, tumours containing 25-30% macrophages (e.g., chemically induced sarcomas) are highly susceptible to B.c.G. therapy, whereas those containing only 2-3% macrophages (e.g., mammary carcinomas) are less responsive. Most importantly, our findings

growth by this

1.

D. L., Eilber, F. R., Holmes, E. C., Cancer Immun. Immunother. 1976, 1, 93.

Morton,

Sparks,

F.

C., Ramming, K. P.

Merrin, C., Han, T, Klein, E., Wajsman, Z., Murphy, G. P Cancer Chemother. Rep. 1975, 59, 157. 3 Pimm, M. V., Baldwin, R. W Br J. Cancer (in the press). 4. Moore, M, Lawrence, N., Nisbet, N. W. Int. J Cancer, 1975, 15, 891. 5 Pimm, M. V, Baldwin, R. W. Nature, 1975, 254, 77. 6. Hopper, D. G, Pimm, M. V., Baldwin, R. W. Cancer Immun. Immunother. 1976, 1, 143. Chassoux, D., Salomon, J.-C Int J. Cancer, 1975, 16, 515. 8 Baldwin, R. W. Transplant. Rev. 1976, 28, 62.

2

7